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- SPRING 13 U: Design of multifunctional nano-obj... http://www.emrs-strasbourg.com/index.php?option=com_content&task=... 1 sur 2 06/05/2013 09:37 SPRING 13 U: Design of multifunctional nano-objects for biomedical applications The fast growing research in nanoscale science and nanotechnology has brought many potential opportunities as well as challenges in innovations in medicine. It is revolutionizing the field of diagnosis and therapy. A great part of current researches in the field aims at designing functional nano-objects displaying therapeutic and diagnostic functions which can identify disease states and deliver therapy. Scope: The symposium aims at presenting the latest developments in the synthesis and the processing of multifunctional bioactive nano-objects, as well as their biomedical applications. The research on advanced biomedical nano-objects needs an interdisciplinary approach because of the involvement of different synthetic methodologies (organic, organo-metallic, inorganic and physical approaches) and of biomedical applications. In this symposium, we will focus on the design, synthesis and characterization of multifunctional nano-objects and on their biomedical applications. The main objectives of this symposium will be the following: a) to bring together chemists (inorganic, organic, polymer, solid state), biologists, biochemists, engineers and clinicians active in the field of new nano-objects for biomedical applications (imaging, targeting, drug delivery, therapeutic ) b) to focus on the design and fabrication of nano-objects leading to advanced bioactive multifunctional materials, c) to analyze the relationship between the nano- object and the biomedical response, d) to establish the state of the art in the field and to open perspectives for the development of new multifunctional nano-objects for biomedical applications. Original Research and Review Papers can be submitted to be published in a special issue on Functional Nanoparticles for Biomedical applications in Nanoscale, Impact factor 5.9. The deadline for submission is 30th of April 2013. Please see the link for more details and submission: http://blogs.rsc.org/nr/2012/09/05 /functional-nanoparticles-for-biomedical-applications/ Hot topics to be covered by the symposium: Design, synthesis and characterization of nanoparticles: inorganic, polymers, liposomes, dendrimers. Biofunctionalisation of nanoparticles Biocompatibility Targeting strategies Drug delivery systems Biomedical Imaging (e.g. MRI, MPI, SPECT, PET) Therapeutics (e.g, hyperthermia, curie theraphy) Diagnostics (e.g., enzymatic assay, immunoassay, biosensing) Biodistribution/bioelimination Nanotoxicology List of invited speakers (confirmed): Nadine Millot, France: Development of novel theranostic platforms: from titanate nanotubes to SPIONs, advantages and comparison with other nanostructures Beatriz Hernandez, Spain: Nano-objects based on semiconductor nanocrystals Maximo Masserini, Italy: Nanoparticles for therapy and diagnosis of Alzheimer Disease Ricardo Bentes de Azevedo, Professor of Nanobiotechnology, Brasil Francesco Stellaci, Professor of Materials Science at EPFL, Switzerland Sébastien Lecommandoux, France: Smart polymer vesicles for therapy and diagnosis: toward multifunctional biomimetic nanomedicines Robert Muller, Belgium: The design of nanoparticles for molecular imaging: a multidisciplinary task Christine Menager, France: Magnetic hybrid systems for nanomedicine applications Ijeoma Uchegbu Delphine Felder-Felsch, France Soo-Jin Choi, Korea Antonios Kanaras, UK Dhirendra Bahadur, India Fernando Herraz, Spain Scientific Committee: Jean-Marie Devoisselle, France Dhirendra Bahadur, IIT Bombay, India Q.A. Pankhurst, UK Ingrid Hilger, Germany Kannan Krishnan, USA Christian Plank, Germany Kerry Chester, UK Jon Dobson, USA Mathias Brust, UK

- SPRING 13 U: Design of multifunctional nano-obj... http://www.emrs-strasbourg.com/index.php?option=com_content&task=... 2 sur 2 06/05/2013 09:37 Sponsor: Symposium organizers: Nguyen TK Thanh Department of Physics and Astronomy University College London Davy Faraday Research Laboratory The Royal Institution of Great Britain London W1S 4BS UK Phone: +44 207 491 6509 ntk.thanh@ucl.ac.uk http://www.ntk-thanh.co.uk Etienne Duguet Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB) 87 ave du Dr Albert Schweitzer F-33608 Pessac Cedex France Phone: +33 540 002 651 duguet@icmcb-bordeaux.cnrs.fr Puerto Morales Instituto de Ciencia de Materiales de Madrid Consejo Superior de investigaciones Cientificas Sor Juana Ines de la Cruz 3 28049, Madrid Spain Phone: +34 913348995 Puerto@icmm.csic.es Claire Billotey Laboratoire de Physico-Chimie des Matériaux Luminescents UMR 5620 CNRS-UCBL Université Claude Bernard Lyon 1 10 rue Ada Byron 69622 Villeurbanne cedex France Phone: +33 4 72 11 62 61 Claire.billotey@univ-lyon1.fr Sylvie Begin Institute of Physic and Chemistry of Materials of Strasbourg (IPCMS) 23, rue du Loess, BP43 67034 Strasbourg cedex France Phone: +33 3 88 10 71 92 Sylvie.begin@ipcms.unistra.fr European Materials Research Society 23 Rue du Loess - BP 20-67037 Strasbourg Cedex 02 - France - Phone:+33-(0)3 88 10 63 72 - Fax:+33-(0)3 88 10 62 93 - emrs@emrsstrasbourg.com

1 sur 25 06/05/2013 09:29 PROGRAM VIEW : 2013 Spring MY PROGRAM : 2013 Spring Symposium : U Design of multifunctional nano-objects for biomedical applications 27 May 2013 28 May 2013 29 May 2013 30 May 2013 31 May 2013 hide a start at Subject Num. Polymer-based systems 1 : D. Felder - S. Begin-Colin 09:00 Biomimetic polymersomes for therapy and diagnosis Authors : Colin Bonduelle, Julie Thévenot, Hugo Oliveira, Maité Marguet, Olivier Sandre, Sébastien Lecommandoux Affiliations : Université de Bordeaux, IPB-ENSCBP, 16 avenue Pey Berland, 33607 Pessac Cedex, France, CNRS, Laboratoire de Chimie des Polymères Organiques, UMR5629, Pessac, France Resume : Polymer vesicles (polymersomes) are among the most attractive systems for drug delivery applications. Actually, vesicles obtained by self-assembly of block copolymers are expected to overcome some of the current limitations in drug delivery, allowing the development of robust nanocontainers of either hydrophilic or hydrophobic species. In addition, the development of macromolecular nanodevices that can be used within the living body implies that sensors detecting chemical signals -such as ions, enzymes or ph changes- and generating internal signals or appropriate responses be integrated in the macromolecular system (1). The use of peptide and saccharide building blocks in the copolymer structure would allow both controlling the self-assembled structure and the resultant biofunctionality. We report an overview on the self-assembly in water of amphiphilic block copolymers into polymersomes, and their applications in loading and controlled release of both hydrophilic and hydrophobic molecules and biomolecules. We pay special attention to polysaccharide and polypeptide-based block copolymer vesicles that we have studied these recent years in our group (2,3). These newly developed copolymers that mimic the structure and function of glycoproteins represent an example of the effectiveness of a biomimetic strategy in implementing materials design (4). In addition, magnetic polymersomes, including iron oxide γ-fe2o3 nanoparticles are currently investigated, together with their poten 09:30 Effective intracellular delivery of proteins and antibodies into mammalian cells using a polymeric delivery system Authors : Postupalenko V., Sibler A.P., Desplancq D., Weiss E., Zuber G. Affiliations : Laboratoire de Pharmacie Biogalénique, CNRS (UMR 7199), Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin 67401 Illkirch, France; Laboratoire de Biotechnologie et signalisation cellulaire, CNRS (UMR 7242), Ecole supérieure de biotechnologie Strasbourg, 300 Boulevard Sébastien Brant 67412 Illkirch, France Resume : Recent advances in biotechnology have led to therapeutic monoclonal antibodies able to mediate a benefit to patients by targeting extracellular receptors. Expending the therapeutic scope of antibodies will depend on our ability to develop specialized delivery systems that can successfully shuttle them into the cytoplasm for targeting intracellular pathology-mediating proteins. Several methods have been described for introducing membrane-impermeable proteins into cells. Direct mechanical/physical membrane destabilizing techniques like electroporation, microinjection or pore-forming reagents showed effective. Alternatively, it is possible to keep the integrity of the plasma membrane by exploiting endocytic pathways through the formation of delivery systems. In this work, we present a multifunctional polymer (πpei) with excellent intracytosolic protein delivery activity. This polymer is able to entrap proteins in stable polyplexes, which are then uptaken by cells via endocytosis. Acidification of the polyplex-contained endosomes in turn led to self-dissociation of the polyplex and membrane rupture, leading to effective translocation. Our current study was notably performed using a potential therapeutic neutralizing monoclonal antibody directed against the intracellular E6 oncoprotein. Our result showed πpei to deliver the anti-e6 into HPV-16 infected 1 1 1 2

2 sur 25 06/05/2013 09:29 CaSki cells as seen by a resurgence of nuclear p53 and may open novel therapeutic perspectives for antibodies. 09:45 Biomacromolecular micro/nanoparticles assembled via isobutyramide groups Authors : Damien Mertz (a,b) and Frank Caruso (c) Affiliations : a: IHU de Strasbourg; b: INSERM U1121 Biomaterials, Strasbourg; c: The University of Melbourne Resume : The development of polymeric nanoparticles has become central to many applications in Nanomedecine. There are however few methods allowing the efficient fabrication of particles made of biological macromolecules. A key challenge is to develop simplified and powerful approaches to design novel particles with improved properties compared with existing methods in terms of biodegradability, toxicity and processing. In coll. with the Univ of Melbourne (Prof. F. Caruso), we pioneered an inedited approach based on the property of isobutyramide (IBAM) grafts to assemble non-covalently, particles composed of proteins, DNA or polysaccharides without the need of an additional cross-linking or other adjuvant. The process consists in a single adsorption step of such biopolymers onto silica templates prealably grafted with IBAM groups or derivatives (e.g., bromoisobutyramide, BrIBAM) followed by template removal.[1] This approach yielded to the formation of bioresponsive hollow capsules and particles made of a range of proteins, nucleic acids and polysaccharides and without loss of their biofunctionality.[2,3]. [1] D. Mertz, P. Tan, Y. Wang, T. K. Goh, A. Blencowe, F. Caruso, Advanced Materials 2011, 23, 5668. [2] D. Mertz, J. Cui, Y. Yan, G. Devlin, C. Chaubaroux, A. Dochter, R. Alles, P. Lavalle, J. C. Voegel, A. Blencowe, P. Auffinger, F. Caruso, ACS Nano 2012, 6, 7584. [3] D. Mertz, H. Wu, J. S. Wong, J. Cui, P. Tan, R. Alles, F. Caruso, Journal of Materials Chemistry 2012, 22, 21434. 1 3 10:00 Coffee break Nanoparticle pharmacokinetics, biodistribution and biodegradation : S. Lecommandoux - C. Billotey 10:30 Effects of particle size and surface chare on pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles in rats Authors : Young-Jung Lee, Hee-Jeong Paek, Hae-Eun Chung, Jeong-A Lee, Mi-Kyung Kim, and Soo-Jin Choi Affiliations : Department of Food Science and Technology, Seoul Women s University Resume : Zinc oxide (ZnO) is one of the most commonly utilized materials in diverse industrial fields such as dyes, paints, pigments, metallurgy additives, rubber, alloys, ceramics, chemical fibers, electronics, catalyst, medical diagnosis, sunscreens, cosmetics, personal care products, and food additives. The wide range of applications of ZnO is attributed to their unique characteristics, including semiconducting, electrical, optical, catalytic, magnetic, antimicrobial and ultraviolet light absorption properties. However, study on the toxicological effects of ZnO nanoparticles in biological systems has lagged behind the speed of their mass production and applications in various fields. Moreover, a few studies have investigated the pharmacokinetics of nanoparticles in whole animals, including absorption, distribution, metabolism, and excretion patterns at the systemic level. In this study, pharmacokinetics, tissue distribution, and excretion of ZnO nanoparticles were evaluated in male and female rats after oral administration. Effects of particle size (20 and 70 nm) and surface charge (negative or positive) were also investigated. The results showed that ZnO nanoparticles of different size and charge were not easily absorbed into the bloodstream via the gastrointestinal tract after a single oral dose. The liver, lung, and kidney could be possible target organs for accumulation and toxicity of ZnO nanoparticles independent of particle size, surface charge, or gender. The nanoparticles were mainly excreted via the feces, and smaller particles were cleared more rapidly than the larger ones. ZnO nanoparticles at a concentration below 300 mg/kg were distributed in tissues and excreted within 24 hours. These findings provide crucial information on possible acute and chronic toxicity of ZnO nanoparticles in potential target organs. 11:00 Intravascular behaviors of layered nanomaterials according to their size, morphology and surface charge Authors : Hyoung-Mi Kim1, Byung Chul Jung2, Yoon Suk Kim2*, Jae-Min Oh1* Affiliations : 1Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Gangwondo 220-710, Korea; 2Department of biomedical laboratory science, College of Health Sciences, Yonsei University, Wonju, 2 1 2 3

3 sur 25 06/05/2013 09:29 Gangwondo 220-710, Korea Resume : Layered double hydroxide (LDH) nanomaterial, which consists of mixed metal hydroxide nanolayers and interlayer anions, is one of attractive candidates in drug delivery system researches for intravenous injection. In this study, we have evaluated the biological behaviors of LDH nanomaterials in blood vessels with respect to their physicochemical properties such as particle size, morphology and surface charge. LDH nanomaterials with controlled size and morphology were prepared by regulating crystal growth mechanism through hydrothermal treatment or urea hydrolysis. And the surface charges of LDHs were manipulated by adjusting the metal ratio of LDH lattice. Powder X-ray diffraction patterns and scanning electron microscopic analyses indicated that all the prepared LDHs possess hydrotalcite-like structure with desired size and morphology; ~ 40, ~ 150 and ~ 350 nm size with spherical shape or ~ 2000 nm size with plate-like morphology. According to zeta potential measurement, the surface charge was determined to be well controlled depending on composition. In order to evaluate the possible interaction of LDHs with human blood components, we investigated the hemolytic and protein fluorescence quenching effect of differently prepared LDHs. The surface interaction between LDHs and blood cells was visualized by optical or electron microscopy after Wright staining. 11:15 Comparative study of nanoparticles size analysis using different characterization techniques Authors : Amina Tijani-Wirth1, Bert De Roo1, Alexander Schwamberger2, Leander Dillemans1, Jin Won Seo3, Lutz Bruegemann2, David Jacob4 and Jean-Pierre Locquet1 Affiliations : 1Department of Physics and Astronomy, KU Leuven, Leuven, Belgium; 2Bruker AXS, Karlsruhe, Germany; 3Department of Metallurgy and Materials Engineering KU Leuven, Leuven, Belgium; 4Cordouan Technologies, Pessac, France; Resume : Nanoparticles (NP) are widely used in research and industry to tailor and improve materials properties. These properties depend on the composition, shape, size and size distribution of the incorporated NP. Therefore, a precise determination of size and size distribution is a major challenge with regard to structure property relations. Among the methods frequently used for the characterization of NP, only a few are applicable, i.e. SAXS and DLS. SAXS can be used to analyze dispersions and powders, whereas DLS is limited to dilute solutions. For comparison, TEM is also used for local information on size and shape of NP. In this work, a comparative study on NP size using SAXS, DLS and TEM is reported. Commercial NP made of Au, SiO2 and polystyrene with sizes ranging from 10 to 200 nm are selected. A nearly perfect coincidence between SAXS and TEM is observed for all NP. DLS shows larger sizes and size deviations depending on the type of materials. This study fully supports the view that comprehensive information on size and shape require more than one characterization technique. No single method allows a full characterization of NP in their natural, physiological environment. To achieve a complete picture of NP morphology, a combination of methods is required. An online measurement using a combination of DLS and SAXS or DLS and UV-vis will be presented. The applicability of online size measurements for monitoring and controlling the process of NP formation will be discussed. 11:30 PEG modified nanoparticles: pharmacokinetics and biodistribution. Authors : Amalia Ruiz1,2, Yenisel Hernández3, Carlos Cabal3, Evelio González3, Sabino Veintemillas-Verdaguer1, Eduardo Martínez3, María del Puerto Morales3 Affiliations : 1 Departamento de Biomateriales y Materiales Bioinspirados, Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Cantoblanco, 28049 Madrid, Spain. 2 Centro de Estudios Avanzados de Cuba, San Antonio de Los Baños km 3½, La Habana, Cuba. 3 Centro de Ingeniería Genética y Biotecnología, Ave. 31/158 and 190, La Habana, Cuba. Resume : Superparamagnetic iron oxide nanoparticles (NP) have been proved to be highly effective contrast agents for magnetic resonance imaging diagnosis [1]. Some of these particles have been modified with Polyethylene glycol (PEG) resulting in nanoparticles with long circulation times, low toxicity and immunogenicity. Given the advantages of using these materials, it is worth studying the influence of PEG coating on the pharmacokinetics and biodistribution of iron nanoparticles. In this study we obtained magnetite nanoparticles (12 nm) via thermal decomposition of a coordination complex as iron precursor [2]. Particles were coated with meso-2,3-dimercaptosuccinic acid (DMSA) and conjugated to polyethylene glycol-derived molecules (PEG) by EDC. Using a rat model and intravenous injection, we explore the nanoparticle biodistribution pattern in different organs (liver, spleen and lungs). The time of residence in blood measured from the NMR relaxivity values and the Fe content was doubled for PEG coated nanoparticles and consequently particle accumulation in liver and spleen was reduced. Histological analyses showed no alterations in organs and confirmed the 2 4 2 5

4 sur 25 06/05/2013 09:29 magnetic measurements and iron quantification results about the heterogeneous distribution of NPs in the organs. MRI in vivo studies confirm that no exist any organ alteration. Furthermore, several NP kinetics parameters like the absorption, residence and excretion time and velocities in the rat s liver were been determinate by in vivo MRI. Findings indicate that PEG modified nanoparticles are a promising platform for diagnosis and drug delivery. References 1. Laurent S, et al. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 2008; 108: 2064-110. 2. Salas G, et al. Controlled synthesis of uniform magnetite nanocrystals with high-quality properties for biomedical applications. J Mater Chem 2012; 22: 21065. 11:45 Biodegradability of superparamagnetic nanoparticles of iron oxide used as MRI contrast agents in organic tissue and intra-cellular environments. Authors : Alexandre Tamion1, Valentin-Adrian Maraloiu1, Fabien Chaveau2, Hugo Rositi2, Arnaud Hillion1, Matthias Hillenkamp1, Marie-Geneviève Blanchin1, Marlène Wiart 2 and Véronique Dupuis1 Affiliations : 1 Institut Lumière Matière, UMR5306 Université Lyon1-CNRS, F-69622 Villeurbanne cédex 2 CREATIS UMR CNRS 5220 U1044 Inserm, F-69677 Bron cédex Resume : In nanomedecine, ultrasmall superparamagnetic particles of iron oxide (USPIO) are used as MRI contrast agents for variety of applications. However, there is few data available about the biotransformation of USPIOs after their intravenous administration. Metabolic changes include the transformation of USPIO core into ferritin. In this paper, our aim is to present an efficient technique based on magnetic susceptibility measurements and simulations, to reach a statistical determination of both magnetic nanoparticles differentiated by their magnetic size and phase. Indeed, we recently developed an accurate triple fit analysis method where the zero-field cooled/field cooled (ZFC/FC) curves and a room temperature magnetization loop are simultaneously adjusted using a semi-analytical model to determine particle magnetic size distribution, moment and anisotropy. Magnetometry measurements have been performed on dehydrated samples of liver and spleen of healthy C57B16 mice after USPIO injection (P904 from Guerbet laboratory) at clinical dose (50 µmol/kg) and sacrifice up to 3 months later. By fitting the entire curves, no appreciable USPIO modification has been detected up to 2 weeks, while continuous magnetic signal degradation is observed from 1 to 2 months with a stabilisation of the number of USPIO which are still present in organs up to 3 months. In parallel, sophisticated HR-TEM and STEM-HAADF experiments allow us to identify the temporal transformation of USPIO into ferritin. 2 6 12:00 Lunch Drug Delivery systems : Soo-Jin Choi - Nguyen TK Thanh 13:30 Designing Nanomedicines Authors : Ijeoma Uchegbu Affiliations : UCL School of Pharmacy Resume : Our laboratory is concerned with the nanofabrication of medicines in order to overcome specific drug delivery challenges. We have focused on the delivery of hydrophobic compounds and of neuropeptides. Nanoenabled medicines are termed nanomedicines and are constructed from the self assembly of amphiphilic polymers and amphiphilic peptides. The morphology, size and functional aspects of the resulting self assembled nanoparticles are controlled by the chemistry of the amphiphiles, with amphiphiles being dialled up from particular molecular architectures. These nanomedicines facilitate the oral absorption of hydrophobic drugs and peptides. Particles act by being taken up in the gastrointestinal tract via the enterocytes and are found in the liver and other organs. The blood brain barrier usually hampers drug delivery to the brain and peptide brain delivery is particularly difficult as peptides are destroyed in the blood and enjoy very short half lives. Using this polymer based nanoparticle technology, peptides are delivered to the brain on oral and intravenous administration, via a well understood mechanism. Finally nanofibres have been constructed from self assembled amphiphilic peptides and these nanofibres are able to deliver peptides to the brain in situations where the peptide alone is not delivered to the brain at all. 3 1

5 sur 25 06/05/2013 09:29 14:00 Magnetic silica nanospheres as drug delivery systems by a supercritical fluid route Authors : N. Murillo-Cremaes1, J. Saurina2, P. Subra-Paternault3, C. Domingo1, A. Roig1 Affiliations : 1Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus de la UAB, Bellaterra, Spain. 2Universidad de Barcelona, Dpt. Analytical Chemistry, Campus UB, Barcelona, Spain 3Université Bordeaux, CBMN UMR 5248, Bat B14 bis, Allée Geoffroy St Hilaire, 33600 Pessac, France Resume : A current challenge in materials science is the design of functional nanostructured materials combining superior properties with reliable processing technologies. Among nanostructured materials, nanoparticles with complex architectures are gaining prevalence in industrially relevant products and very especially in the field of nanomedicine. Therefore, the development of greener strategies with the potential to scale-up materials production is of paramount importance. Gathering special attention is the investigation of processes free of organic solvents to avoid undesired toxic effects of many organic solvents and of their side products. In this context, the use of supercritical fluids as a reaction media is worth to be considered [1]. This technology is becoming very attractive in chemical synthesis due to properties such as zero surface tension, mass transfer characteristics (diffusivity and viscosity) similar to those of gases, and density and solvation power more similar to liquids. Here, we will demonstrate the versatility of supercritical fluids by using them in several processing steps. Firstly, a novel strategy using a sol-gel assisted supercritical fluid method to synthesize biocompatible iron oxide-silica composite nanospheres that could find their use both in diagnosis (MRI) and in therapy (magnetically guided drug delivery) will be presented [2]. The intrinsic porosity of the nanospheres in combination with the chemical versatility of the silica offered a suitable environment to host active molecules. In a second step, a model drug -an anti-platelet agent- was first dissolved in supercritical carbon dioxide and then entrapped within the silica matrix. We have proved that these matrices provide enhanced stabilization of the drug against hydrolysis [3]. In addition, the release profile of the therapeutic agent in both acidic (ph=2, as stomach) and neutral (ph=7.4, as bloodstream) media has been analyzed by High Performance Liquid Chromatography. Results show a very fast release kinetics in which 100% of the therapeutic agent is released within the first 10 minutes. A progressive sustained released of the drug, during 5 hours, could be achieved by further coating the nanospheres with selected biopolymers, once more, using supercritical fluids. 14:15 Nanostructural and Optical Studies on Biodegradable Drug Delivery Systems Authors : M. Gioti, V. Karagkiozaki, A. Basgiouraki, P.G. Karagiannidis, S. Logothetidis Affiliations : Lab for Thin Films Nan systems and Nanometrology (LTFN), Physics Department, Aristotle University of Thessaloniki, Thessaloniki, GR-54124, Greece Resume : In recent years, there is an emerging interest on the development of specially designed systems for controlled drug delivery meeting specific biomedical applications. Thin film biodegradable polymers with appropriate nanostructural properties can exhibit the desired gradual degradation defined by the demands of drug-eluting implants. In this work, we design and develop biodegradable polymeric matrices either in multilayer configuration or blended single layer forms using poly(dl-lactide-co-glycolide) of different contents of lactide:glycolide, and polycaprolactone to serve as drug reservoirs with mul tiplex loading capacities for cardiovascular and retinal implants. Spin coating technique is applied for the films growth. An antiplatelet drug; dipyridamole, and an antibiotic one; dexamethasone, are also encapsulated with spin coating into the polymeric matrices. The surface morphology and the optical and compositional properties of the as-grown films are investigated by Atomic Force Microscopy (AFM) and Spectroscopic Ellipsometry (SE). Ex-situ AFM and SE studies at ambient environmental conditions are used for the assessment of the degradation characteristics of the systems upon their incubation in phosphate buffered saline (PBS) at specific sampling times. Additional in-situ and real-time ellipsometric studies are realized during their immersion in PBS for the dynamic characterization of the polymer degradation, nanostructural modifications and drug elution. 14:30 Cellular internalization and trafficking of ligand decorated nanoparticles: drug delivery perspective Authors : S Stolnik, D Vllasaliu, E Moradi, R Fowler Affiliations : Drug Delivery and Tissue Engineering Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD Resume : The work in our group has been focused on the cellular internalization and intracellular trafficking of surface decorated nanoparticles, particularly the decoration with ligands that promote receptor-mediated internalization in the lung and the intestines, with the view of exploring such systems for delivery of biologicals to or across these epithelial tissues to achieve local or systemic 3 2 3 3 3 4

6 sur 25 06/05/2013 09:29 therapeutic effect, respectively. This work has shown that, for instance, ligand surface density and ligand distribution pattern ( clustering ) determine cellular internalization of folate decorated nanoparticles (RSC Advances 2, 3025), whereby with an increase in ligand density the cellular internalization pathway of nanoparticles shifts from predominantly clathrin to filipin-mediated, while clustered ligand presentation promotes nanoparticles internalization, relative to a disperse presentation. The data also show that folate ligand promotes nanoparticles transcytosis across the model epithelium. We also, for the first time, demonstrated that Fc-region of IgG can be applied as a ligand to promote cellular internalization and transcytosis of decorated nanoparticles in epithelial cells and that such a system is capable of shuttling a therapeutic antibody (Journal of Controlled Release 158, 479). Recent work demonstrated that a ligand attachment to nanoparticles does not necessary result in the system adopting the same cellular pathway as the functionality alone, whereby vitamin B12 surface attachment to 50 nm nanoparticles changes the natural clathrin mediated internalization of the vitamin to predominantly caveolae-mediated (submitted Small). These entry pathways play essential role in determining downstream intracellular processing of nanoparticles and hence their drug delivery potentials. These aspects will be further addressed in the presentation. 14:45 Hybrid thermo-responsive iron oxide nanoparticles for hyperthermia mediated drug delivery Authors : Hamilton Kakwere, Manuel Pernia-Leal, Pablo Guardia Giros, Maria Materia and Teresa Pellegrino Affiliations : Hamilton Kakwere; Manuel Pernia-Leal; Pablo Guardia -Giros; Maria Materia; Istituto Italiano di Tecnologia (IIT). Via Morego, 30 16163 Genova, Italy Teresa Pellegrino;National Nanotechnology Laboratory of CNR-NANO, Via per Arnesano, 73100 Lecce (Italy) and Italian Institute of Technology, via Morego 30, 16163, Genova (Italy) Resume : As cancer deaths continue to rise worldwide, there has been a significant push towards the design of effective anti-tumor drug delivery systems. Most efforts have focused on the preparation of stimuli-responsive nanosized polymeric drug carriers which ensure on demand drug release at the tumor site. We have prepared hybrid nanoparticles incorporating iron oxide nanocubes (core) and thermoresponsive polymer (shell) which can act as anti-tumour drug delivery vehicles. Iron oxide nanocubes were chosen for their exceptional high specific absorption rate. Using living radical polymerization techniques, iron oxide nanocubes were singly decorated with a shell of poly(n-isopropyl acrylamide-co-polyethylene glycol acrylate) yielding water soluble particles of about 100 nm. The thermo-responsive behavior of the nanoparticles was ascertained via turbidimetric analysis and their phase transition temperature varied with monomer composition. The nanoparticles were loaded with doxorubicin which could be released upon increasing the temperature above the lower critical solution temperature of the polymer (> 37 C). We demonstrate that these hybrid nanocarriers have the ability to release drugs on demand by exploiting the capability of iron oxide nanocubes to generate heat under alternating magnetic field (AMF). By controlling the LCST of the polymer, the nanocarriers prepared exhibited a non-significant drug release below 37 C but showed a consistent release of their cargo under AMF. 15:00 Design of Enzyme responsive nanoparticles and capsules Authors : Clemens K. Weiss, Adrian, V. Fuchs, Mattias Maier, Julien Andrieu, Niklas Kotman, Volker Mailaender, Katharina Landfester Affiliations : Max Planck Institute for Polymer Research, Germany Resume : In this contribution we present the preparation of protease responsive nanoparticles and capsules, based on the integration of protease cleavable peptide sequences in polymeric systems. Optical detection of enzymatic cleavage is achieved by framing the peptide sequence with a fluorophore-quencher pair resulting in an internally quenched fluorescence peptide (IQF-peptide). Upon cleavage the fluorescence is recovered. Three strategies were used to integrate the sequences in to polymeric nanostructures resulting in particulate or capsule systems with sizes below 500 nm. Particles were created either via crosslinking of poly(styrene-co-acrylic acid) with the peptide sequence in inverse miniemulsion or by synthesizing a hydrophobic triblockcopolymer of the structure polystyrenepeptide-polystyrene and subsequent nanoprecipitation. Nanocapsules were prepared by a polyaddition reaction of lysine-terminated peptide sequences and a diisocyanate at the droplet interface in inverse miniemulsions. The structures were physicochemically characterized an incubated with the enzymes. Even integrated into the nanostructures, enzymes (trypsin and hepsin) were able to cleave the respective sequences and encapsulated dye was released from the capsules upon enzymatic cleavage of the sequence. The possibility to use hepsin, which is a protease expressed in the early stages of prostate cancer highlights the potential of 3 5 3 6

7 sur 25 06/05/2013 09:29 the presented nanosystems for the early detection of prostate cancer. 15:15 Functionalized Mesoporous Silica Nanoparticles as Drug Delivery System for Poorly Soluble Drugs Authors : Mathieu Varache, Florence Bouyer, Igor Bezverkhyy, Rémi Chassagnon, Nicolas Geoffroy, Lucien Saviot, Florence Baras, Frédéric Bouyer Affiliations : Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303, Dijon, France; Université de Bourgogne, INSERM UMR 866, Dijon, France Resume : Drug delivery systems (DDSs) have been developed for a few decades in cancer chemotherapy to reduce the side-effects induced by anticancer drugs. These carriers reduce accumulation in the normal tissues either by specific targeting due to grafting of ligand moieties or by non-specific targeting due to the EPR effect. Since 2001, inorganic DDSs have received attention, especially MCM41 mesoporous silica nanoparticles (MCM41-MSNs). In this study, MCM41-MSNs have been synthesized using sodium hydroxide-catalyzed reactions of tetraethoxysilane (TEOS) in the presence of a cationic surfactant (CTAB). MSNs were functionalized using various silanated organic moieties by a co-condensation approach either to control the particle loading or to study the internalization of the MSNs in cancer cells. A thorough control of the synthesis parameters leads to stable suspensions of monodisperse MCM41-MSNs. The MSNs were functionalized in situ with silanated PEG and a new strategy was developed to extract CTAB. The resulting MSNs remain stable in physiological fluid for several days. Native and functionalized MSNs are not toxic up to 100 µg/ml in the presence of human colic SW480 cancer cells. Fluorescence and confocal microscopy experiments suggest the internalization of the nanoparticles into cancer cells. In our communication, we will present these results and other findings concerning the loading and release profiles of a poorly soluble drug, cisplatin in the presence of modified MSNs. 15:30 Nanoshell-coated fluorescent proteins as safe fluorescent probes and drug carriers Authors : Aoneng Cao, Yu Yang, Ying Liu, Haifang Wang Affiliations : Shanghai University Resume : Along with the rapid development of nanotechnology, nanoparticle (NP)-based fluorescent probes, such as quantum dots (QDs), show high potential to replace the traditional organic dyes. A major merit of nanoprobes is that they also provide platform to carry multiple molecules such as targeting groups and therapy drugs to achieve the drug delivery and therapeutic response monitoring simultaneously. However, one of the major concerns for current nanoprobes such as QDs is its bio-safety. Even after coated by various biocompatible shells, the toxic heavy-metal in QDs is still a big biohazard, especially for long-term in vivo applications. Therefore, safer nanoprobes are in high demand. Fluorescence proteins (FPs) are a set of powerful tools widely used in life sciences. But they are generally used as reporter genes. FPs are not suitable and have seldom explored as external probes, because of the unstable nature of proteins. We show that encapsulating FPs in NPs would make them safe and robust external probes. The nano shell not only protects FPs from denaturation and metabolic digestion, but also enhances the quantum yield and photostability of the wrapped FPs. In addition, this new kind of nanoprobes can be easily made multifunctional for drug delivery. 15:45 Contrast agents based on Prussian blue analogues Authors : G. Paul, N. Dia, Y. Prado, L. Sancey, P. Perriat, O. Tillement, S. Laurent, L. Vander Elst, R. Muller, T. Mallah and L. Catala Affiliations : ICMMO,Université Paris Sud, Orsay, France LPCML, UMR 5620 CNRS, Université Lyon 1, France INSA-Lyon, UMR 5510 CNRS, Université de Lyon, France NMR and Molecular Imaging Laboratory, Université Mons Hainaut, Belgium Resume : Coordination chemistry offers the possibility to tailor in metal-based coordination polymers/networks new platforms at the nanoscale designed for diagnosis or biomedical applications. This communication will focus on nanoparticles of Prussian blue analogues (PBA) based on FeIII and MnII that can be tuned a will, with an excellent control over size protected by biocompatible polymers. Relaxivity measurements performed on the aqueous dispersions of Prussian blue «full» particles and core-shells show r1 values that are coherent with a participation of the FeIII sites located not only at the surface of the particles but in the more internal layers. In the case of the MnII-based PBA nanoparticles, large relaxivities have been observed at very low MnII content, due to a location of the MnII ions at the periphery of the particles. Good contrasts have been obtained for the smaller 6 nm PB nanoparticles and 25% MnII PBA nanoparticles. Cell internalizations have been followed through fluorescence confocal microscopy for the two series of nanoparticles. The advantages offered by these original nano-objects will be discussed. 3 7 3 8 3 9

8 sur 25 06/05/2013 09:29 Poster session : - 16:00 Nanoparticle microinjection and Raman spectroscopy as tools for nanotoxicology studies Authors : Patrizio Candeloro, Luca Tirinato, Natalia Malara, Victor Puntes, Gerardo Perozziello, Francesco Gentile, Maria Laura Coluccio, Enzo Di Fabrizio, Affiliations : BioNEM Laboratory, Experimental and Clinical Medicine Department, University Magna Graecia of Catanzaro, Catanzaro, Italy; Institut Catala' de Nanotecnologia and Institut Catala' de Recerca i Estudis Avancats (ICREA), Barcelona, Spain; Resume : Microinjection techniques and Raman spectroscopy have been combined to provide a new methodology to investigate the cytotoxic effects coming from the interaction of nanomaterials with cells. In the present work, this novel technique has been used to investigate the effects of Ag and Fe3O4 nanoparticles on Hela cells. The nanoparticles are microinjected inside the cells and these latter ones are probed by means of Raman spectroscopy after a short incubation time, in order to highlight the first and impulsive mechanisms developed by the cells to counteract the presence of the nanoparticles. The results put in evidence a different behaviour of the cells treated with nanoparticles in comparison with the control cells that are not injected. The difference Raman spectra between the treated and non-treated cells are compared with a Raman database of main biomolecules, finding that the differences are mainly due to a decreased content of glycogen in the treated cells. This effect is supposed to be generated by an emerging oxidative stress due to the presence of nanoparticles. Finally, cells are also microinjected with only the solvents of nanoparticles and they show no cytotoxic effects, thus ensuring that the observed toxicity is not due to the microinjection itself or to the solvents. The achieved results demonstrate the suitability of the proposed method as a new tool for nanotoxicity studies. 16:00 Development of Iron Oxide Superparamagnetic Sensors for Cardiovascular Nanomedicine Authors : B.Salinas, J. Ruiz-Cabello, F. Herranz Affiliations : Advanced Imaging Unit. Dpt of Epidemiology, Atherothrombosis and Imaging. Spanish Cardiovascular Research Centre (CNIC) and Spanish Pulmonary Research Centre (CIBERES) Resume : Magnetic Resonance Relaxometry (MRM) and Magnetic resonance imaging (MRI) are increasingly accessible techniques for in vitro and in vivo diagnosis and quantification. Compared to other techniques they are unique for their spatial resolution and lack of ionizing radiation. With this in mind we have developed two types of iron oxide nanoparticulate sensors for the detection and quantification of two important biomarkers in several cardiovascular diseases; Ca2+ ions and Matrixmetalloproteases 2 and 9 (MMPs). By the use of different functionalisation techniques we have obtained nanoparticles that change their response in MRM and MRI in the presence of these biomarkers. We will show how the nanosensor for Ca2+ shows a total selectivity towards calcium compared to other ions (Mg2+, NH4+, Zn2+, Cu2+, Na+) and that the nanoparticles for the quantification of MMPs are capable of detect concentrations of proteins as low as 1 ng/ml, together with selectivity towards MMP-2 and 9. Finally we will show the possibilities of both nanosensors for in vivo detection. 16:00 Biocompatibility and corrosion properties of biomedical magnesium plasmaimplanted with chromium and oxygen at different implantation frequencies Authors : Ruizhen Xu, Xiongbo Yang, Penghui Li, Xuming Zhang, Chenxi Wang, Shaofei Geng, Guosong Wu, Paul K. Chu Affiliations : Department of Physics and Materials Science, City University of Hong Kong, Hong Kong, China Resume : Plasma immersion ion implantation (PIII) is an effective method to modify the corrosion resistance and biocompatibility of magnesium and magnesium alloys. In this work, pure magnesium is modified by dual chromium and oxygen plasma immersion ion implantation (PIII) in an effort to improve the corrosion resistance and enhance the biocompatibility. The depths of the implanted species and thicknesses of the surface oxidized layers are varied by changing the pulsing frequencies during PIII. In order to determine the optimal parameters, the corrosion resistance is determined by electrochemical tests including open circuit potential (OCP) measurements, potentiodynamic polarization tests, and electrochemical impendence spectroscopy (EIS). The adhesion, spreading and proliferation of osteoblasts on the implanted magnesium surface are assessed by cell culture tests. Our results indicate that the surface properties of biomedical magnesium are improved by the dual PIII process. 1 2 3

9 sur 25 06/05/2013 09:29 16:00 Dr Authors : 1. Pola Goldberg Oppenheimer, 2.Johh Robertson, 3. Stephan Hofmann, 4. Sumeet Mahajan Affiliations : 1-3. Department of Engineering, University of Cambridge, UK; 4.Department of Physics, Cavendish Laboratory, University of Cambridge, UK Resume : The highly sensitive and molecule specific technique of surface-enhanced Raman spectroscopy (SERS) generates high signal enhancements via localized optical fields on nano-scale metallic materials, which can be tuned by manipulation of the surface roughness and architecture at the sub-micron level. Carbon nanotubes (CNTs), on the other hand, have been, concurrently, a topic of extensive research and applications, in particular because of their extraordinary electrical, thermal and mechanical properties. However, the application of CNTs for plasmonics including SERS has been only recently beginning to gain interest. We generate low-cost gold functionalized vertically-aligned carbon nanotube forests (VACNTs), which are systematically optimized for their performance as straightforward SERS nano-platforms. Modeling of the VACNT-based SERS substrates reveals consistent dependence on structural parameters as observed experimentally. The created nanostructures span over large substrate areas, are readily configurable and yield uniform and reproducible SERS enhancement factors. These large surface area substrates demonstrate remarkable SERS enhancement factors, up to 10^7 due the high concentration of hot-spots provided by the VACNT forests. Gold-coated small diameter VACNTs forests patterned into pre-designed pillar structures are further utilized for duplex detection demonstrating that patterned VACNTs arrays can act as straightforward and cost-effective substrates for high-throughput multiplex SERS detection. Since vertically oriented CNTs exhibit functionalities such as electrical conductivity and unique adsorption properties, these can be further harnessed in their development as novel chemical and bio-sensing platforms. Based on optimization and developments undertaken, this work also paves the way towards construction and development of fully portable system suited for real time detection focused on areas with a point-of-care need. The unique properties of CNTs, which can be synergistically utilized in VACNT based substrates and patterned arrays, can thus provide new generation platforms for biomedical SERS detection. 16:00 SINGLE-WALLED CARBON NANOTUBES AS POTENTIAL AGENTS FOR ANTIHYPERTENSIVE THERAPY Authors : L.M. Shapoval, V.F. Sagach, S.V. Prylutska, O.V. Dmitrenko, L.G. Stepanenko, L.S. Pobigailo, D.M. Rotko, Yu.I. Prylutskyy, U. Ritter, P. Scharff Affiliations : Bogomolets Institute of Physiology, NAS of Ukraine, Bogomolets Str., 4, 01601 Kyiv, Ukraine; Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64, 01601 Kyiv, Ukraine; Ilmenau University of Technology, Institute of Chemistry and Biotechnology, Weimarer Str. 25, 98693 Ilmenau, Germany Resume : The purpose of the work is to examine the hemodynamic effect of water-soluble single-walled carbon nanotubes (SWCNTs; an initial concentration was 5 µg/ml) depending on the dose and technology of their administration in rats with genetically determined hypertension. In urethane anesthetized rats, SWCNTs were administrated, according to stereotaxic coordinates, in the medullary nuclei (nucleus of solitary tract, NTS; paramedian nucleus, PMn; lateral reticular nucleus, LRN; nucleus ambiguus, AMB) that are directly involved in the nervous control of the vascular tone and cardiac activity. The effectiveness of applied antihypertensive technology was assessed by analyzing the changes in quantitative indicators, such as the systemic arterial pressure (SAP) and the heart rate. Moreover, we have studied the SWCNT toxic effect by analyzing the stability of the erythrocytes to acid hemolysis depending on the dose and the way of SWCNT administration, either intravenous one, or injection in the medullary nuclei using kinetic method. SWCNT injections in the AMB resulted in the SAP drop by 14.4%, in the LRN - by 22.8%, and in the NTS - by 21.6%. Hypotensive responses were characterized by rapid development with maximum in 10-20 s, and they lasted 3 min. In spontaneously hypertensive rats, SWCNT injections resulted in the SAP lowering in the studied nuclei by 22.8%, 21.0%, and 13.0% in the AMB, LRN and PMn, responsively, that is, in those animals responses were usually more significant compared to those in the control rats. Biochemical analysis of the blood samples showed that SWCNTs used did not have toxic effect on the cardiovascular system. The data obtained suggest that SWCNTs are the promising class of pharmaceutical compounds to treat hypertension. 16:00 ANTITUMOR EFFECT OF FULLERENE C60 AND DOXORUBICIN IN VIVO Authors : S. Prylutska, I. Grynyuk, O. Matyshevska, Yu. Prylutskyy, U. Ritter, P. Scharff Affiliations : Joint Ukrainian-German Center on Nanobiotecnology, Taras Shevchenko 4 5 6

10 sur 25 06/05/2013 09:29 National University of Kyiv, Volodymyrska Str., 64, 01601 Kyiv, Ukraine; Technical University of Ilmenau, Institute of Chemistry and Biotechnology, Weimarer Str., 25, 098693 Ilmenau, Germany Resume : Several cytostatics, including doxorubicin (Dox), which is characterized by toxic effect on both transformed and normal cells, are used in the therapy of malignant tumors. Free radicals, which are formed during Dox chemotherapy, inactivate enzymes, responsible for antioxidant protection. C60 fullerene is a biocompatible nanostructure with a potential of free radicals quencher and strong antioxidant. The aim of the study was to evaluate effect of C60 fullerene and Dox on Lewis lung carcinoma growth, metastatic index and activity of antioxidant enzymes in liver and heart of animals with transplanted tumor. A stable water colloid solution of pristine C60 fullerene was used. The presence of C60 clusters with size up to 10 nm was demonstrated by AFM measurement. C60 fullerene (25 mg/kg) and Dox (2.5 mg/kg) both separately and in combination were injected intraperitoneally to mice once a day for 5 days. The extension of tumor-bearing animal life after combined action of C60+Dox was shown to be increased by 30%, while after Dox injection this effect was only 20%. Inhibition of tumor growth was more pronounced at combined action of C60+Dox as compared with Dox treatment only. Cytomorphological study of tumor showed that after Dox treatment the number of mitotic cells was decreased, while after C60+Dox treatment the number of apoptotic cells was strongly increased simultaneously with inhibition of mitotic index. Activity of superoxide dismutase and glutathione peroxidase in liver and heart tissues of animals was found to be depressed after Dox treatment, but at combined injection of C60+Dox it was normalized or even increased. The data obtained confirm tumor-inhibitory effect of fullerene C60 as well as its protective effect against Dox toxicity. 16:00 A Facial Synthesis of Biocompatible Optomagnetic Particles for Application in Photodynamic Cancer Therapy Authors : Woon-phil Baik, Seok-Hong Min, Jin-Seung Jung Affiliations : Myongji University; Gangneung-Wonju National University Resume : We report on the fabrication of biocompatible optomagnetic particles that are strategically designed and prepared by simple modification process. Optical functionality is provided by the hematoporphyrin (HP) which generates singlet oxygen in high quantum yield for photodynamic cancer therapy. The HP molecules are covalently bonded to the surface of cobalt ferrite (CoFe2O4) particle. The magnetic properties of CoFe2O4 particles have been adjusted finely by controlling the size of the primary CoFe2O4 nanograins and the secondary superstructured composited CoFe2O4 particles formed by an aggregation of the nanograins. Microstructure and physical properties of the optomagnetic particles are investigated by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), superconducting quantum interference device (SQUID), X-ray diffraction (XRD) and photoluminescence spectroscopy. The singlet oxygen generation efficiency of the HP being chemically bonded on CoFe2O4 particles was detected by an indirect chemical method by using the decomposition of 1,3-diphenyl-isobenzofuran (DPBF). 16:00 Vapor-Based Multicomponent Coatings for Synergic Double-Click Reactions under Mild Conditions Authors : Meng-Yu Tsai, Tin-Ju Lin, Ching-Yu Lin, Chi-Hui Huang, Jiun-An Gu, Sheng-Tung Huang, Jiash-ing Yu, and Hsien-Yeh Chen Affiliations : Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan Resume : The first maleimide-functionalized poly-p-xylylene is synthesized via chemical vapor deposition (CVD) polymerization from 4-N-maleimidomethyl-[2,2]paracyclophane. The availability of the maleimide functionality is further exploited in combination with alkynyl moiety, and the direct synthesis to prepare the multicomponent coating containing the two functionalities is enabled via CVD copolymerization on various substrates. The novel coating is comprised of distinguished anchoring sites of electron-deficient alkynes and unsaturated maleimides and is readily to simultaneously proceed doubled click reactions. XPS and IRRAS characterizations have verified the chemical composition for the coatings. The demonstration of synergically doubled bioorthogonal reactions is performed via azide-alkyne click reaction and thiol-maleimide coupling reaction to immobilize fluorescently labeled azides and cystines, respectively, under mild conditions in water and without the need of a catalyst, and no trace of crossreaction is found. Finally, the multicomponent surface is designed to exhibit distinct biological functions by first immobilizing polyethylene glycols that provide a low fouling state (bioinert) to suppress undesired background perturbance, while at the same time, addressing surface bioactive function is performed by tethering 7 8

11 sur 25 06/05/2013 09:29 Cys-Arg-Glu-Asp-Val (CREDV) peptides in selected areas and the adhesion and growth of bovine arterial endothelial cells are precisely manipulated. 16:00 AFM NANOMICROGRAPHY WITH APPLICATION TO DENTAL RESINS COMPOSITES Authors : Eduard Gatin (1,2), Roxana Ilici 2, Adriana Balan3, Elena Matei 4, Lidia Ciobanu 5, Ruxandra Sfeatcu 2, Stefan Iordache3, Ioan Patrascu 2 Affiliations : 1 Materials Department, Faculty of Physics, University of Bucharest P.O. Box MG 11, Magurele Bucharest, Romania; 2 University of Medicine Carol Davila, Faculty of Dentistry, Calea Plevnei 19, Sector 5, Bucharest, Romania; 3 University of Bucharest, 3Nano-SAE Research Centre, P.O. Box MG- 38, 077125 Magurele, Romania; 4 INFIM Institute, PO Box MG. 7, Magurele Bucharest, Cod 077125, Romania; 5 St. Pantelimon Hospital, Sos Pantelimon Nr. 340-342, Sector 2, Bucharest, Romania. Resume : Light-cured composites consisting of inorganic fillers and a polymer matrix are increasingly used as dental restorative materials or dental cements, because of their good esthetic and mechanical properties [1 3]. The major problems that affects their performance is the intrinsic polymerization shrinkage and interface adhesion, which are an inevitable effect of the curing process as monomer molecules, converted into a crosslinked polymer network, exchanging van der Waals bonds for shorter covalent bonds [4 5]. This volumetric shrinkage causes stress in confined environments such as tooth cavities [6]. Polymerization shrinkage and the resulting shrinkage stress play an important role in influencing the forces acting on the tooth-restoration interface, because they might reduce the integrity of the restored tooth tissue and might possibly lead to bond failure between the resin and the tooth structure. Debonding may create plastic deformation, marginal leakage, and staining, postoperative sensitivity, and increase the risk of secondary caries formation and pulpal inflammation [7 9]. Strength and toughness are usually investigated by SEM-EDS, microfractography and macro/micro hardness. To understand the process on the above mentioned properties at nanoscale, a series of investigations with AFM revealed local stresses and their dynamics for different conditions of polymerization. This study emphasizes a new perspective for investigation in dental medicine with nano / microfractography, ageing and other secondary factors with AFM beside other structural investigations. Results from this study accomplished with a Raman investigation could predict a model for dentin interface bonding with application as a functional biomaterial. References 1. Ramakrishna S., Mayer J., Wintermanteland E., Leong, K. W., Compos Sci Technol 2011, 61, 1189; 2. Donkerwolcke M., Burny F., Muster D., Biomaterials 1998, 19, 1461; 3. Sideridou I., Tserki V., Papanastasiou G., Biomaterials 2002, 23, 1819; 4. Feilzer, A. J.; De Gee, A.; Davidson, C. Dent Mater 1990, 6, 167; 5. Choi, K.; Condon, J.; Ferracane, J. L. J Dent Res 2000, 79, 812; 6. Braga R. R., Ballester R. Y., Ferracane J. L., Dent Mater 2005, 21, 962; 7. Hashimoto M., Ohno H., Sano H., Kaga M., Oguchi H., Biomaterials 2003, 24, 3795; 8. Mjör I. A., Toffenetti F., Quintessence Int 2000, 31, 165; 9. Camps J., Dejou J., Remusat M., Dent Mater 2000, 16, 432. 16:00 b-cyclodextrin Immobilization onto Silica Surface under Mild Conditions Authors : Nadiia Roik, Lyudmila Belyakova Affiliations : Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine 17 General Naumov Str., Kyiv, 03164, Ukraine Resume : b-cyclodextrin (b-cd) molecule can be regarded as a container for keeping of molecules of another substances. Molecular encapsulation with the participation of b-cd is widely applied in pharmaceutical technologies and analytical methods. However, the use of b-cd for control releasing, separation, extraction of biologically active compounds is complicated by its high solubility in aqueous media. This difficulty can be overcome by chemical immobilization of b-cd on water insoluble support. Silica is the most promising inorganic carrier owing to its high chemical and thermal stability, and also good kinetic parameters. The well known azidation, tosylation, amination, and silanization procedures which are usually realized to activate b-cd macromolecule for subsequent grafting onto silica/organosilica surface, belong to the labor and time consuming syntheses. Alternatively, the primary hydroxyl groups of b-cd can be activated with 1,1'-carbonyldiimidazole (CDI), well known coupling agent, under mild conditions. In the present study, surface grafting of b-cd onto aminopropylsilica was carried out through a three step procedure: synthesis of aminopropylsilica, activation of b-cd with 1,1'-carbonyldiimidazole (CDI), and its following immobilization onto aminopropylsilica surface. The control over all stages of b-cd immobilization was performed by means of IR spectral and chemical analysis of surface layer. The content of chemically immobilized b-cd determined by acid hydrolysis to glucose equals 0.033 mmol/g. It can be assumed that b-cd containing silica will be useful for separation and preferable removing of biologically active compounds, like aromatic amino acids. 9 10

12 sur 25 06/05/2013 09:29 16:00 SYNTHESIS OF BIOCOMPATIBLE DENDRITIC CARRIERS FOR MELANOMA DIAGNOSIS THROUGH SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT) Authors : A. Parat 1 and A. Garofalo1, P. Bonazza2, J. Taleb2, J-M. Chezal3, C. Billotey2 and D. Felder-Flesch1 Affiliations : 1 IPCMS-UMR 7504, 23 rue du Loess, BP 34, 67043 Strasbourg cedex 2, France 2 LPCML-UCBL UMR 5620, Service de Médecine Nucléaire Pavillon B, 5 place d Arsonval, 69437 Lyon cedex 03, France 3 UMR 990 INSERM/Université d'auvergne, 58 rue Montalembert, 63005 Clermont-Ferrand, France Resume : Medical imaging techniques have been tremendously developed during the last century (Single Photon Emission Computed Tomography SPECT, Posion Emission Tomography PET-scan, Magnetic Resonance Imaging MRI, Optical Imaging) in order to find the best treatment to cure the disease, and mainly cancers (1). Since it is well known that cancer growth is linked to metastasis, the detection of its development is one of the main goals of medical imaging research, as it provides an important first step towards a potential treatment. To this end, we have focused our research on melanoma cancer (2, 3) by developing new biocompatible dendritic carriers for SPECT tumor and/or metastasis diagnosis. We will describe the proof of concept of our research using low generation and PEG decorated PAMAM bifunctional carriers through 111In or 99mTc chelation for SPECT imaging of melanoma tumors in mice: tumor uptake is increasing with the number of targeting agents grafted at the periphery of these bifunctional carriers. Moreover, such increase demonstrates the cooperative effect obtained thanks to the dendritic structure as tumor uptake (%) is not linear (more than exponential) with the number of targeting agents. 1 A. Rembielak, M. Green, A. Saleem, P. Price, Medicine, 2011, 39, 693-697 2 W. Tuong, L.S. Cheng, A.W. Armstrong, Dermatologic Clinics, 2012, 30, 113-124 3 D.A Tomalia, A.M. Taylor, W.A. Goddard, Angew. Chem., Int. Ed., 1990, 102, 119-157, F.M. Veronese, G. Pasut, DDT, 2005, 10, 1451-1458 16:00 Preparation and characterization of graphene-modified bone cement for high strength property Authors : Yu-Hsun Nien*, Li-Hong Tai Affiliations : Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin, 640, Taiwan Resume : Bone cement is medical material used in orthopedic surgery such as total hip replacement. Polymethylmethacrylate is used as major material in acrylic bone cement. However, acrylic bone cement has some shortcomings, for example, its poor mechanical strength. The poor mechanical properties of acrylic bone cement result in adverse effects. In this study, we explore the use of adding graphene to acrylic bone cement for preparing high strength and toughness bone cement. The mechanical properties of the bone cement are characterized using tensile and compressive analysis as well as dynamic mechanical analysis (DMA). Through the above test, the results show that the use of graphene is able to improve the mechanical properties of acrylic bone cement. 16:00 biomedical applications Authors : biomedical applications Affiliations : biomedical applications Resume : biomedical applications 16:00 Preparation and characterization of biodegradable conduits with aligned ultra-fine fibrous structures by electrospinning Authors : Yu-Hsun Nien*, Chien-Ju Lu, Ming-Long Yeh Affiliations : Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin, 640, Taiwan; Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin, 640, Taiwan; Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan Resume : Electrospinning is a technique to fabricate nanofiber. As large surface area, high porosity and comparable size with natural materials in body, nanofiber is able to provide cells with configuration for adhesion, proliferation and differentiation. In the applications of tissue engineering, aligned fibrous structures mimicking the natural extracellular matrix morphology are considered promising scaffolds such as nerve conduits. In this study, we (1) design and fabricate biodegradable conduits with aligned ultra-fine fibrous structures by electrospinning of chitosan/poly(caprolactone)/poly(ethylene oxide) and (2) characterize the properties of the biodegradable conduits with aligned ultra-fine fibrous structures. We use fibroblast to observe cell morphology and proliferation on the biodegradable 11 12 13 15

13 sur 25 06/05/2013 09:29 conduits with aligned ultra-fine fibrous structures. The results show that the biodegradable conduits with aligned ultra-fine fibrous structures have potential in the application of artificial cellular conduits. 16:00 Multifunctional PEGylated Ce3+ sensitized GdPO4:Tb3+ nanorods and its composite with Fe3O4 nanoparticles: Investigation of energy transfer process, hyperthermia, bioimaging and drug delivery Authors : Niroj Kumar Sahu, N. Shanta Singh, D. Bahadur Affiliations : Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai-400 076, India Resume : Herein, we report the multifunctional PEGylated Ce3+ sensitized and Tb3+ activated GdPO4 (GdPO4:Tb3+/Ce3+) nanorods and their composite with Fe3O4 nanoparticles for biolabeling, hyperthermia and drug delivery applications. Photoluminescence investigation of GdPO4:Tb3+/Ce3+ shows the occurrence of efficient energy transfer from Ce3+ to Tb3+ giving enhanced green luminescence. The energy transfer process and its efficiency are found to depend on Ce3+ and Tb3+ concentration. The relation to the increase in non-radiative rate possesses from sensitizer to activator by efficient transfer of energy is realized from steady state and time resolved luminescence studies. Luminescence quenching due to cross relaxation is least significant up to Ce3+ (20 at.%) and Tb3+ (7 at.%) concentration. The quantum yield of GdPO4:Tb3+ (5 at.%)/ce3+ (5 at.%) is found to be 25%. Paramagnetic behavior due to Gd3+ ions is observed in both GdPO4:Tb3+ and GdPO4:Tb3+/Ce3+. The nanocomposite of Fe3O4- GdPO4:Tb3+/Ce3+ (1:4) shows no appreciable cytotoxicity in L929, HeLa and MCF-7 cells lines up to 1 mg/ml. Hyperthermia temperature (~43 ºC) under AC magnetic field (335 Oe) could be achieved with 5 mg of this composite per 1 ml of water in 10 min. Laser scanning confocal microscopy confirms the cellular uptake of Fe3O4/Gd0.9Ce0.05Tb0.05PO4 nanocomposite by MCF-7 and its accumulation in the cellular cytoplasm without destroying the cell structure. Further, the PEGylated nanorods are able to load doxorubicin (anticancer drug) upto ~80% during 24 h and shows sustained release. This system could be useful for bio and magnetic resonance imaging, drug delivery as well as for thermal therapy for cancer treatment. 16:00 Dendronized iron oxides as smart nano-objects for multimodal imaging Authors : B. Basly, S. Fleutot, A. Garofalo, C. Ghobril, D. Felder-Flesch, S. Begin-Colin Affiliations : Institut de Physique et Chimie des Matériaux,UMR CNRS-UdS 7504, 23, rue Loess BP 43, 67034 STRASBOURG Cedex 2, FRANCE. Resume : Superparamagnetic iron oxide nanoparticles (NPs) with appropriate surface coating are widely used for numerous in vivo applications and in particular for MRI contrast enhancement. In the biomedical field, most studies are performed for improving the materials biocompatibility and ensuring multifunctionalization, but only a few investigations have been carried out improving the quality of the magnetic NPs (size distribution, effect of their functionalization). Indeed particle size, surface chemical structures and the nature of interactions of the organic coating appear as critical parameters determining the blood half-life, opsonization, biokinetics and biodistributions of magnetic nanocrystals. The main bioactive molecules grafted at the surface of iron oxide NPs will be described as well as strategies for conjugation of molecules and their effect on parameters such as the colloidal stability, biodistribution... Then a synthesis way based on dendritic and phosphonate approaches will be presented: phosphonate groups ensure a strong anchoring of dendron at the NPs surface with preservation of magnetic properties, and dendrons, in addition to their small size, are very promising as the diversity of functionalization brought by the arborescent structure simultaneously may solve the problems of biocompatibility, low toxicity, large in vivo stability and specificity. Iron oxide NPs synthesized by co-precipitation and thermal decomposition were coated with three dendrons bearing PEG chains or carboxylate or amine-functionalized PEG chains to improve colloidal stability, graft fluorescent molecules and investigate cell interactions. Cell viability tests, relaxivity values, biodistribution studies and in-vivo IRM experiments have demonstrated the low toxicity of these dendronized nanoparticles and their interest as contrast agent. 16:00 New magnetic sensitive nanocomposites biopolymer-based networks: design and mechanical properties under magnetic field Authors : A. Ponton, C. Galindo-Gonzalez, S. Gantz, S. Ammar-Merah, F. Mammeri, L. Oury Affiliations : University Paris-Diderot Paris 7 & CNRS MSC Laboratory Itodys Laboratory Resume : In the past few years there has been increased interest in the development of stimuli-responsive polymer materials of emerging applications. In particular magnetic polymer networks are a new class of soft polymer materials with the properties controlled by magnetic field. In this context we elaborated new 16 17 18

14 sur 25 06/05/2013 09:29 magnetic sensitive nanocomposites biopolymer-based networks by introducing functionalized magnetic nanoparticles in uncrosslinked aqueous solutions of sodium alginate which is a biocompatible, biodegradable and untoxic linear copolymer bearing carboxylate group (COO- ionized form) in the media of neutral or basic ph. Iron oxide nanoparticles were synthesized on the basis of hydrolysis and condensation reactions of iron acetate in a polyol solvent and water. The functionalization of these nanoparticles was achieved by using two bifunctional organic ligands that grafted to the surface of the nanoparticles either by complexation of ions Fe3+ or by linkages Si-O-Fe through sol-gel process. The development of a new original device allowed the measurements of mechanical properties under continuous magnetic field in order to determine structure and dynamical properties at various external conditions [1]. We have clearly demonstrated reversible modulation of low shear and viscoelastic properties of new magnetic sensitive nanocomposites biopolymer-based networks opening new perspectives of applications for these materials. [1] The project was funded by 7th Framework Programme of the European Communities (http://www.physique.univparis-diderot.fr/magbiomat 16:00 Plasmonic metal nanostructures for biomedical applications Authors : O.M. Ivanyuta, Ya.I. Kishenko, V.V. Matvienko Affiliations : Taras Shevchenko National University of Kyiv, Ukraine, 01601 Resume : Interest in metal nanostructures stems from their unique optical properties related with single-particle or collective plasmons. Thе aim is focused on optical properties of gold nanorods and silica/gold nanoshells, whereas the synthesis protocols and biomedical applications are discussed shortly. The effects of the gold nanoshells structural polydispersity and the surface electron scattering in a thin metal layer on the resonance light scattering spectra are studied theoretically and experimentally for the silica/gold nanoshell water colloids. Both the gold nanorods and nanoshells are exceptionally biocompatible nanomaterials, which surface can be easily functionalized by key probe molecules such as antibodies, oligonucleotides, biotin. Finally, we provide an illustration of erythrocyte and living bacteria imaging with silica-gold nanoshells as resonance-scattering labels. In this case, nanoshells are seen as bright red dots against a dark background, except for yellow areas of aggregation, where nanoshells are in close proximity and the plasmon resonance wavelength is changed. 16:00 Uptake and cytotoxicity of silica nanoparticles with different surface functionalizations Authors : A. KURTZ-CHALOT 1,2, V.FOREST 1,2, J. POURCHEZ 1,2, D. BOUDARD 2,3, V. BIN 3, G. BRAGA 4, M. MARTINI5, D. BERNACHE 1, M. COTTIER 2,3. Affiliations : 1 Ecole Nationale Supérieure des Mines, CIS-EMSE, LINA EA 4624, 42023 Saint-Etienne, France; 2 LINA Laboratoire Interdisciplinaire d étude des Nanoparticules Aérosolisées, F-42023, Saint-Etienne, France; 3 PRES Lyon, IFR INSERM 143, Université Jean Monnet, Laboratoire d Histologie CHU, Saint-Etienne, France; 4 PRES Lyon, Centre de Microscopie Confocale Multiphotonique Université Claude Bernard, Villeurbanne, France; 5 LPCML, UMR 5620 CNRS, Université de Lyon, Université Claude Bernard, Villeurbanne, France. Resume : Silica nanoparticles (NP) are particularly interesting for medical applications because of their inertness and chemical stability. However, their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological effects of silica nanoparticles depending on their physico-chemical features. We especially focused our attention on the impact of surface functionalization on cytotoxicity. To that purpose, three kinds of fluorescent (FITC) silica nanoparticles were used: 1) steric stabilized NP coated with neutral PEG molecules, 2) positive charge NP stabilized coated with amine groups and 3) negative charge NP stabilized coated with carboxylic acid groups. Nanoparticles were put in contact with the RAW 264.7 murine macrophages. The uptake of NP was assessed by fluorimetry. Finally the cellular response was evaluated in terms of cytotoxicity (loss of cell membrane integrity, determined by the Lactate DeHydrogenase (LDH) assay), inflammation (production of TNF ) and oxidative stress (Reactive Oxygen Species (ROS) generation). Results showed that steric stabilized nanoparticles were more internalized and induced more pro-inflammation compared to charge stabilized nanoparticles. However, these latter, even less internalized triggered more oxidative stress. In conclusion, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and cytotoxicity. 19 20

15 sur 25 06/05/2013 09:29 16:00 Bacterial cellulose films to evaluate nanoparticles and cells. Authors : Muling Zeng, Anna Roig, Anna Laromaine Affiliations : Institut Ciencia de Materials de Barcelona, Campus UAB, 08193 Bellaterra, Spain. Resume : Extensive research efforts have recently been directed toward the synthesis and characterization of inorganic nanoparticles to generate novel materials and devices potentially useful for sensing, catalysis, transport, imaging and other applications in medicine and engineering science. For such applications, the ability to control and tune the performance of nanoparticles (NPs) at biological relevant conditions is critical. Cells respond differently according to the environment where they reside, for instance endothelial cells cultured in a three dimensional environment (3D) exhibit a tubular shape whereas on a petri dish (a 2D surface), they form monolayers. The evaluation of NPs and its interaction with cells is lengthy and costly although critical to achieve its final medical application. Assays to provide useful biological information at lower cost and at early stages of the NP development, and to generate fundamental knowledge and drive technological development in the longer term are in high demand, and in light of the performance of cells in 3D we believe NPs should be assessed also in 3D environments. Here, we present the characterization and production of cellulose films of less than a hundred microns thick produced by Glucoacetobacter bacteria. These thin films are processed using three different drying methods: 1) room temperature, 2) freeze drying and 3) supercritical drying. The different processes confer to the cellulose films a variety of porosity, flexibility and strength that can be tailor and control for different applications. In the final part of the talk, we would illustrate how we could use the cellulose scaffolds to assess viability, functionality and toxicity of NPs and cells in 3D environments. 16:00 Grafting of a thermosensitive polymer onto the surface of iron oxide nanoparticles Authors : A. Hannecart [1], S. Laurent [1], O. Sandre [2], D. Stanicki [1], S. Miraux [3], S. Lecommandoux [2], L. Vander Elst [1] and R. N. Muller [1,4] Affiliations : [1] NMR Laboratory, Organic Chemistry Department, University of Mons, B-7000 Mons, Belgium; [2] Laboratoire de Chimie des Polymères Organiques (LCPO- UMR5629), CNRS, ENSCPB, Université Bordeaux 1, 33607 Pessac-Cedex, France; [3] Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS / Université Bordeaux Segalen Bordeaux France; [4] Center for Microscopy and Molecular Imaging, B-6041 Charleroi, Belgium Resume : Thanks to their high magnetic moment, iron oxide nanoparticles lead to a Magnetic Resonance Imaging (MRI) contrast enhancement by accelerating the relaxation of water protons. However, surface modification of iron oxide nanoparticles with silanes showed a significative decrease of relaxivity (efficiency as contrast agents for MRI) with the increase of the thickness of the coating. This observation is of paramount importance in the context of the development of contrastophores for molecular imaging and could be explained by a restricted access of water molecules to the magnetic core. To confirm this hypothesis, a thermosensitive polymer, Jeffamine M-2005, was grafted onto the surface of iron oxide nanoparticles. Jeffamine M-2005 is characterized by a lower critical solution temperature (LCST) in water around which it undergoes a reversible transition. Below the LCST, Jeffamine M-2005 is soluble in water but becomes insoluble upon heating above the LCST. Therefore, the surface of the obtained nanoparticles reversibly changed from hydrophilic below the LCST to hydrophobic above it. As expected, these nanoparticles are characterized by a decrease of relaxivity once the LCST of Jeffamine is reached due to the formation of a hydrophobic coating surrounding the nanoparticles. This decrease of relaxivity above the LCST of the thermosensitive polymer grafted onto iron oxide nanoparticles could be used for the design of a temperature-responsive contrast agent. 16:00 EVALUATION OF THE ANTIMICROBIAL ACTIVITY OF STRYPHNODENDRON BARBATIMAN AGAINST CITROBACTER FREUNDII: A MORPHOLOGICAL STUDY Authors : Nara C. de Souza, Márcio N. Gomes, Rafael R. G. Maciel, Romário Justino da Silva, Tarquin F. Trescher,Josmary R. Silva, Affiliations : Grupo de Materiais Nanoestruturados, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil Resume : Medicinal plants have been presented as a valuable source of preservation of human health. Stryphnodendron barbatiman has been employed due to its antimicrobial activity. S. barbatiman is rich in tannins and has been used in popular medicine for treatment of gastrointestinal disorder, treatment of lesions, and anti-inflammatory as well as antimicrobial agent. Citrobacter freundii is a member of the Enterobacteriaceae family and is the major cause of opportunistic infections. This microorganism is a bacterium (bacillus) aerobic gram-negative with a length in the range 1-5 m. C. freundii are commonly found in water, soil, food 21 22 23

16 sur 25 06/05/2013 09:29 and occasionally in the gastrointestinal tract of animals and humans. Here, we present the evaluation of the antimicrobial activity of S. barbatiman by observing the inhibition halo and investigating biofilm formation of C. freundii and S. barbatiman on solid surfaces using a combination of spectroscopy (UV-vis and IR) and atomic force microscopy. Our results suggest that S. barbatiman avoid bacterial growth probably though a damage mechanism on cellular wall. 16:00 Docetaxel loaded hydrophobically derivatized hyperbranched polyglycerol nanoparticles for intravesical bladder cancer therapy Authors : Clement Mugabe, Richard T. Liggins, Yoshiyuki Matsui, Alan I. So, Martin E. Gleave, Donald E. Brooks, Helen M. Burt Affiliations : Centre for Drug Research and Development, 2405 Wesbrook Mall, Fourth Floor, Vancouver, BC V6T 1Z3, Canada; Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Centre for Blood Research; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Resume : Introduction & Objectives: Development of novel therapeutics for patients with non-muscle-invasive bladder cancer is an important topic considering the rather limited options currently available. Treatment failure is thought to be in part due to the short dwell-time of intravesical drugs and the low drug uptake in the bladder wall. The objective of the present work was to evaluate the effectiveness of intravesical nanoparticulate docetaxel (DTX) in an orthotopic model of bladder cancer. Methods: DTX was loaded into hydrophobically derivatized hyperbranched polyglycerols (HPG-C8/10-MePEG) by a solvent evaporation method. Human urothelial carcinoma cell lines were treated with various concentrations of DTX formulations in vitro. Mice with established KU7-luc tumours were given intravesical instillations with vehicle controls, Taxotere or DTX (0.5 mg/ml) loaded HPG-C8/10-MePEG nanoparticles. Results: In vitro, DTX loaded HPG-C8/10-MePEG nanoparticles were found to have equivalent cytotoxicities as the commercial formulation of Taxotere. In vivo, DTX loaded HPG-C8/10-MePEG nanoparticles significantly inhibited tumour growth (97% tumour inhibition, p<0.001) in an orthotopic model of bladder cancer. The amount of DTX in the bladder tissues from these subjects was about three-fold higher than those instilled with Taxotere. Conclusions: Our data show promising in vivo antitumor efficacy and provide preclinical proof-of-principle for the intravesical nanoparticulate DTX. 16:00 Interaction and stability of chlorophyll BSA complexes Authors : Filipe D.S. Gorza, Graciela C. Pedro, Tarquin F. Trescher, Marli L. Moraes, Josmary R. Silva, Nara C. de Souza Affiliations : Grupo de Materiais Nanoestruturados, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil Resume : Interactions between proteins and drugs, which can lead to formation of stable drug-protein complexes, have important implications on several processes related to health. Consequently, these interactions can affect the distribution, free concentration, biological activity, and metabolism of the drugs in the blood stream. One approach to investigate the interaction mechanisms between proteins and drugs is to study the physical-chemical properties of a solid state system model such a casting film. Bovine serum albumin (BSA) is an essential extracellular protein which can be found in high concentration in blood plasma. The multiple binding sites associated to exceptional ability of BSA to interact with many organic and inorganic molecules, becomes this protein an important regulator of intercellular stream as well as the pharmacokinetic behavior of many drugs. On the other hand, chlorophyll (Chl) has been used historically in the treatment of several human conditions with no evidence of human toxicity. Recently, it has been shown that this molecule exerts an antimutagenic behavior against a wide range of potential human carcinogens. Here, we report on the UV-visible spectroscopic examination about the interaction of BSA with Chl in aqueous solution under physiological conditions. Structural information regarding the binding constants and the effects on the protein structure are provided. Films were obtained by the casting technique in order to investigate the formation of complexes by using optical microscopy. 16:00 Self-associating polyethylenimines with a ph sensitive disassociation switch upon sensing endosomal acidity lead to effective in vivo oligonucleotide delivery systems Authors : Guy Zuber, Benoit Frisch Affiliations : CNRS, Université de Strasbourg, UMR 7199 Faculté de Pharmacie 74, route du Rhin 67400 Illkirch France Resume : Synthetic oligonucleotides are highly specific modulators of the genetic information and may provide huge benefits in medicine. The oligonucleotides have unfortunately poor pharmacological properties and rely on multifunctional carriers 24 25 26

17 sur 25 06/05/2013 09:29 for protection in biological fluids but also for cell anchorage and for crossing the cell membrane to reach their molecular target. In here, we report the integration of a novel functionality to polyethylenimine (PEI), a polymer possess already sirna binding, cell anchorage and endosomytic functions. The results led to an innovative class of polymer with excellent oligonucleotide delivery properties. The aqueous soluble PEI was equipped with various hydrophobic elements to stabilize the sirna/polymer system through hydrophobic polymer to polymer self-association. These polymers were then evaluated for sirna delivery ability. The results showed the most active hydrophobic PEIs to self-dissociate at endosomal ph, leading to favored sirna intracellular release at time when the proton-sponge property of PEI exerts its endosomolytic activity. A leading polymer (named πpei), with low hemolytic activity and an excellent activity/toxicity index was evaluated further in an in vivo human glioblastoma tumor model. A single injection of 100 nm πpei/sirna system led to 50 to 30% sirna-mediated gene silencing and substantiates the potential of this class of multifunctional, yet chemically simple, carrier for therapeutic application of oligonucleotides. 16:00 Capping ligand design for the metal oxide colloidal particles to be used as imaging agents and carriers Authors : Galina Goloverda, Denis Nilov, Pavel Kucheryavy, Vladimir Kolesnichenko Affiliations : Xavier University Chemistry Department New Orleans, Louisiana 70125 USA Resume : The performance of magnetic nanoparticles as imaging and targeted delivery agents strongly depends on the properties of the surrounding organic shell. Biocompatible small-molecule organic ligands, which would make the organic layer around the nanocrystals just thick enough for providing the desired colloid stability, would be ideal for good magnetic response and high mobility of the resulting composite in live cells. The idea is that the targeted ligand will covalently bind to the surface of a mineral core at several sites, so that the cooperative effect of several groups would provide strong binding constant of the constructed adduct, and therefore its resistance to hydrolysis. Magnetite nanoparticles (4-5 nm) obtained in a colloidal form by high-temperature hydrolysis of iron(ii,iii) chelated alkoxides in homogeneous diethylene glycol solutions were studied with a series of polydentate small-molecule ligands and corresponding adducts were isolated. Acid-base titrations were accompanied by Dynamic Light Scattering and electrokinetic mobility measurements using Malvern Zetasizer Nano ZS instrument. The products of organic syntheses after purification were characterized by 1H NMR, 13C NMR, electrospray MS (acids) and GC-MS (esters). Colloidal magnetic nanoparticles were found to be effectively stabilized by small-molecule polydentate α-hydroxyacids, which can effectively replace the currently used polymers. The advantages are: (a) magnetic properties of the composite would not be degraded by large diamagnetic contribution from macromolecules; and (b) diffusion through different biological tissues would be significantly enhanced. 16:00 Stabilization TiO2 and decrease its cytotoxic properties Authors : Elena V. Bessudnova, Zinfer R. Ismagilova, Nadezhda V. Shikina, Elena I. Ryabchikova Affiliations : Boreskov Institute of Catalysis; Boreskov Institute of Catalysis, Institute of Coal Chemistry and Material Science; Boreskov Institute of Catalysis; Institute of Chemical Biology and Fundamental Medicine Resume : A method to produce stable titanium dioxide sols with anatase phase and a narrow particle size distribution of 3-5 nm has been developed. We have investigated the particle ability to penetrate into different cell cultures and their cytotoxic effects. TiO2 nanoparticles have demonstrated an active penetration into cultivated cells through endocytosis without additional transfection methods disturbing the cell membrane. A method of chemical treatment of sols has been developed to increase the stability of the dispersed and biosafety TiO2 nanoparticles at neutral ph. Sols have been examined by a set of physicochemical methods (XRD, Raman-spectroscopy, SAXS, AFM, TEM, measuring ζ-potential). The ultrathin sections of MDCK cells treated with TiO2 nanoparticles prepared by different methods have been examined by TEM. The effect of the chemical nature of the monovalent electrolyte (LiOH, NaOH, KOH, NH4OH), surface modification by glycidyl isopropyl ether (GE), the order of reagent additions and conditions of dialysis in the neutralization step of sols on their dispersion and cytotoxic properties has been determined. It has been shown that nanoparticles with GE does not cause a change in the morphology of the cell structure and do not damage the cell membrane. The cytotoxic effect has been investigated in vitro. Nanoparticles modified with GE have been shown to exhibit low cytotoxicity, and after 2-6 hours of exposure TiO2 nanoparticles with cells the number of dead cells is comparable to that of the intact cells. 27 28

18 sur 25 06/05/2013 09:29 16:00 A kilogram-scale synthesis methodology of ferrite nanoparticles for environmental and biomedical applications Authors : K. Simeonidis (1), M. Perissi (2), M. Angelakeris (2), M. Mitrakas (3), G. Vourlias (2), N. Andritsos (1) Affiliations : (1) Department of Mechanical Engineering, University of Thessaly, 38334 Volos, Greece; (2) Department of Physics, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (3) Analytical Chemistry Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece Resume : The preparation of magnetic ferrite nanoparticles by the co-precipitation of metal salts in aqueous environment includes a number of advantages compared to other chemical or mechanical methods when environmental or biomedical applicability is of interest. Among them is the extremely low cost, the possibility of working at room temperature, the absence of toxic byproducts and the feasibility of working in water. In this work, we examine the heating efficiency under AC field of 29 MFe2O4 nanoparticles (M=Fe, Co, Mn, Cu, Mg, Ni) produced by this method at alkaline environment. To establish a better control of the synthetic parameters (acidity, redox), the method was adapted to a continuous flow arrangement and scaled-up for industrial-scale production. Depending on the nature of metal salts and the temperature of reaction, the hyperthermia properties may be optimized according to the conditions of application (frequency, field). For instance, inhibition of structural vacancies in Fe3O4 nanoparticles improves efficiency at high frequencies whereas better results at low frequencies are observed when intermediate complexation takes place during synthesis. Environmental issues related to the avoidance of NH3 use and metal leaching during application are also discussed. This work was implemented within the framework of Action Supporting Postdoctoral Researchers of Operational Program Education and Lifelong Learning (Action s Beneficiary: GSRT), and is co-financed by ESF and Greek State. 16:00 Elucidation of the Unique Optoelectronic Properties of Pt@Ag Nanoparticles for Tailorable Biomolecular Probes Authors : Dao Thi Ngoc Anh, Daisuke Hotta, Derrick Mott, Shinya Maenosono Affiliations : Japan Advanced Institute of Science and Technology Resume : Platinum is a well-known catalyst that has a high catalytic activity, especially for methanol electrooxidation and oxygen electroreduction reactions. In the developed tendency, platinum has been combined with numerous possible metals, such as Pd, Au, Fe, Cr, Ni, etc. in purpose to increase electrocatalysis and limit the poisoning of Pt surface by strongly adsorbed intermediates (e.g CO). Among those combinations, Pt-Ag system has been received much attention from researchers and scientists for not only electrocatalytic activity but also surfaceenhanced Raman scattering. However, there are still many challenges in the synthesis of core@shell structures. Galvanic replacement reaction is the difficulty in synthesizing Ag@Pt core@shell, while successful formation of Pt@Ag core@shell must overcome lattice mismatch. This oral focuses on our recent results in the study of Pt@Ag core@shell NPs with controllable size and shell thickness. In addition, the plasmonic properties and unique electronic structure of this system can give us the wide road in future for catalytic, SERS and the others applications. The results are discussed in terms of UV-Vis, XRD, TEM, HR-TEM, EDS, XPS, and HAADF-STEM. 16:00 PHOTODYNAMIC INACTIVATION AND SURFACE MORPHOLOGICAL CHANGES ON CITROBACTER FREUNDII BY USING ERYTHROSINE DYE AND LASER LIGHT Authors : Josmary R. Silva, Gleidson Cardoso, Rafael R.G. Maciel, Nara C. de Souza Affiliations : Grupo de Materiais Nanoestruturados, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil Resume : The battle against diseases caused by bacteria commonly uses therapies based on antibiotics. A huge problem of this approach is the resistance developed by some bacteria to these drugs over time. An alternative strategy to the use of antibiotics is antibacterial photodynamic therapy (PDT). This method is based on inactivating the bacteria cellular death by employing a photosensitising compound and a light source in the presence of oxygen. In this work, photodynamic inactivation (PDI) of the Citrobacter freundii bacterium, using erythrosine dye (Ery) as photosensitizer and 532 nm laser light, was demonstrated by employing the colony count method. The effectiveness of the PDI was found-be ~ 80%. UV-Vis spectroscopy showed photodegradation of Ery, suggesting the presence of reactive oxygen species (ROS), which were associated to PDI. FTIR spectroscopy indicated that the irradiation leads to cell wall damage without the presence of Ery. This may allow a penetration of Ery into the bacteria and thus increasing the effectiveness of the PDI. Analysis of atomic force microscopy (AFM) of films prepared from C freundii + Ery showed morphological changes of the surfaces of bacteria after irradiation. These changes were attributed to cell damages of the outer membranes 30 31

19 sur 25 06/05/2013 09:29 of C. freundii as a result of the PDI. This study indicated that the strategy of using the combination of Ery and laser light of 532 nm (PDI) may be feasible to develop a photodynamic therapy against diseases arising from the C. freundii. 16:00 Nanocarriers based on biodegradable polyphosphazenes Authors : Ian Teasdale, Sandra Wilfert, Oliver Brüggemann Affiliations : Institute for Polymer Chemistry, JKU Linz, Austria Resume : The use of synthetic polymers for drug-delivery has become a wide-spread technique to enhance the bioavailability and specificity of smallmolecules drugs. However, the long-term use of non-degradable high-molecular weight polymers above the renal clearance limit is of concern. This is especially so if, as for example with anti-cancer drug delivery, high amounts of polymer and repeated doses are required. There is, therefore, a pressing need to develop polymers with controlled biodegradability that can be repeatedly administered without prolonged accumulation in the body. Although there are clearly a number of potential biodegradable polymers available, inorganic-organic hybrid poly(organo)phosphazenes offer a number of distinct advantages, not least their completely degradable backbone to non-toxic degradation products. Due to recent developments in their polymer synthesis polyphosphazenes can be prepared with controlled molecular weights and narrow polydispersities. They also possess inherently high functionality, two-functional groups per repeat unit, which can be exploited to prepare polymer therapeutics with covalently bound drugs, solubilizing groups and targeting ligands and/antibodies. Furthermore, it allows the facile tuning of amphiphilic polymers which can self-assemble into nanoparticles. Two applications which represent the versatility of polyphosphazenes for drug delivery are summarized in this contribution, namely the coupling of traditional anthracycline chemotherapeutics via ph labile bonds to the polymers, as well as, in separate work, the conjugation of the photoactive agent hypericin for its use in photodynamic therapy. The synthetic routes are briefly portrayed, as well as their preparation as polymer-drug conjugates. Detailed in-vitro studies show both the excellent biocompatibility of the polymeric carriers and their degradation products, as well as the activity of the attached drugs. 16:00 Viability of biomembranes from latex with propolis for clinical applications Authors : Angélica J. Silva, Josmary R. Silva, Nara C. de Souza, Paula C. S. Souto Affiliations : Grupo de Materiais Nanoestruturados, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil Resume : There has been a growing interest in materials based on natural rubber (NR) for a variety of reasons, ranging from use of these materials in renewable sources to biomedical applications. In addition, recent findings have confirmed the suitability of NR derivated systems for regenerative medicine, in which the angiogenic properties of the NR latex are exploited, and in drug delivery systems. Propolis is a resinous material collected by bees from plant sources which exhibits antimicrobial, immunemodulatory and anti-inflammatory activity. In Brazil, besides wide variety of flora there are also several bees species among which stand out those belonging to Meliponinae subfamily, known as indigenous stingless bees. In this group are found the bees of the Scaptotrigona genus and we have used the propolis collected by this kind of bees. This work aimed to prepare and characterize a system formed by NR matrix and propolis extract, which was incorporated into the matrix. In this system, we have investigated the changes morphological, aging, wettability, and antimicrobial activity as a function of the propolis incorporation. 16:00 Optical studies of interactions between II-VI semiconductor nanoparticles and proteins Authors : A.I. Savchuk, I.D. Stolyarchuk, T.A. Savchuk, V.V. Makoviy, O.A. Savchuk Affiliations : Department of Physics of Semiconductors and Nanostructures, Chernivtsi National University, 2 Kotsubynsky Str., 58012 Chernivtsi, Ukraine Resume : In the past decade, semiconductor nanoparticles (NPs) have attracted great attention in area of biomedical research. For such kind of applications the interactions of NPs with model proteins type of bovin serum albumin (BSA) or human serum albumin (HSA) play important role [1-3]. The advantage of semiconductor NPs for biomedical applications are size-dependent emission spectra, high quantum yield, multicolor excitation, surface functionality and good photostability. In this work, we report on comparative studies of interactions between II-VI semiconductor NPs and model proteins type of BSA and HSA. For this purpose, UV-vis absorption, luminescence and Faraday rotation spectra were investigated. The obtained results show the changes of protein luminescence spectra after adding of semiconductor NPs in appropriate solution. These changes are similar to those from data of recent publications [2-3]. First of all the quenching of luminescence from HSA and BSA was observed after adding of NPs. The 32 33 34

20 sur 25 06/05/2013 09:29 quenching effect is the most prominent for CdTe NPs with bigger average size (about 5 nm). The UV-vis absorption spectra of the proteins have also changed because of complex formation (for instance, between HSA and NPs). Additionally, adding of Mn-doped CdS NPs to HSA gives evidence for quenching of emission band, which is due to the 4T1(4G)-6A1(6S) transition of Mn2+ ions. The results on Faraday rotation spectra are more informative for Mn-doped II-VI semiconductor NPs. In this case, influence of the added proteins on s,p-d spin exchange interactions can be extracted. The obtained data are important for further evaluation of the toxicity of semiconductor NPs. 1. X. Zhang et al., Nanotechnology,22 (2011) 195501; 2. Q. Xiao et al., J.Photochem. Photobiology A: Chemistry, 249(2011)53; 3. Q. Xiao et al., Colloids and Surfaces B: Biointerface, 102 (2013) 76. 16:00 Micropatterns of SiNWs Directing Neurite Growth of PC12 Cells Authors : Yu-Ning Kuo, Hsin-I Lin, Tzu-Wei Wang, Hsieh-Ting Wu, Ta-Jen Yen Affiliations : Institute of Nanoengineering and Microsystems, National Tsing-Hua University; Department of Materials Science and Engineering, National Tsing-Hua University Resume : Numerous therapies to treat serious nervous imperfections have been developed by repairing the nervous system and patterning neurons. However, the effectiveness of the reported therapies is limited by the uncontrollability of electrical conductivity and poor cell adhesion. Herein we demonstrated micropatterned n-sinws fabricated by the electroless metal deposition method as an effective solution to uniformly guide the neurite growth, with further advantages of simple and low-cost fabrication, controllable conductivity, adjustable wettability and non-cytotoxicity. Our results suggest that the superhydrophilic n-sinws are a promising non-cytotoxic material as a fact that as culturing L929 cells and PC12 cells atop, those cells induce rich filopodia and lamellipodia to firmly attach to the tips of the n-sinws. In contrast, hydrophobic Si3N4 and flat Si (n-, p- and undopped types) strongly resist cell adhesion instead. In addition, on the micropattern of 1 m-long n-sinws in the 5 m-wide trench during cell differentiation, PC12 cells become larger and exhibit obvious neurite extensions along the SiNWs region. Therefore, such conductive and hydrophilic micropatterned n-sinws can effectively guide neurite growth, functioning as a platform for studying the fundamentals of cell biology and neuron regeneration. 16:00 Enzymatically synthesized multi-functional PHA nanoparticle for theranostic applicaitons Authors : Sung-Geun Jung, Hee-Su Kwon, Young-Rok Kim Affiliations : Department of Food Science and Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea Resume : Efficient delivery of imaging agents and drugs to the targeted disease site is one of the most crucial requirements in clinical diagnosis and treatment, which requires superior detection and targeting methods. To achieve this goal, we have developed theranostic nanoparticles using PHA synthase enzyme fused with green fluorescent protein (GFP) and colon cancer specific single chain variable fragment antibody (A33scFv). PHA synthase was employed to produce biodegradable and biocompatible nanoparticle that is suitable for drug delivery. A33scFv was selected as the targeting moieties since they have a specific affinity to the A33 antigen, which is abundantly expressed on the surface of colon cancer cells. GFP was also employed as an imaging agent for visual diagnosis of cancer cell. The resulting construct, A33scFv::gfp::PHA synthase was overexpressed in E.coli Rosseta gami and was further purified by affinity chromatography on Ni-NTA agarose bead. The PHA synthase fused with GFP and A33scFv retained catalytic activity and subsequently used to produce an amphiphilic tri-fusion protein-polymer hybrid with a specific end-functionalities. The resulting amphiphilic protein-polymer hybrid was readily self-assembled into a nanomicelle with GFP and A33scFv displayed on the surface. The specificity of the fluorescent multi-functional PHA nanoparticle toward colon cancer cell lines, SW1222 (A33+) and HT29 (A33-), were visualized and quantified in vitro. This new approach will provide wide applications in effective diagnosis and specific delivery of drug to the target cancer cells. 16:00 Photoisomerization of congo red encapsulated by DPPC vesicles as a possible approach for release control in drug delivery Authors : Filipe D.S. Gorza, Romário J. da Silva, Tarquin F. Trescher, Graciela C. Pedro, Kennedy C. S. Correa, Marli L. Moraes, Josmary R. Silva, Nara C. de Souza Affiliations : Grupo de Materiais Nanoestruturados, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil Resume : Drug delivery systems consisting of drugs encapsulated by lipid vesicles have attracted significant interest in recent years due to possibility of their use in biomedical applications. Of particular interesting in these systems are the 35 36 37

21 sur 25 06/05/2013 09:29 approaches used to release the drug from vesicle. Congo red (CR) is an azobenzene derivate, which is able to exhibit photoisomerization change of its geometric shape in space by the action of light. In this process, CR molecules can move by trans-cis-trans cycles and affecting its environment. The purpose of this work was exploring the photoisomerization of azobenzene derivated congo red (CR) as a way for releasing drugs contained within dipalmitoyl phosphatidylcholine (DPPC) vesicles. Since CR has absorption peak at about 500 nm, vesicle structure dependence on CR photoisomerization (that can provides insights about the drug release) was induced by using a 532 nm laser irradiation and analyzed with atomic force microscopy. Our results suggested that the CR photoisomerization can affect the vesicle structure and, therefore, this approach has a potential to be employed in drug delivery systems. 16:00 to be submitted to Q:Bionanomaterials for imaging, sensing and actuating Authors : Anita K. Peacock, Solene I. Cauet, Arthur Taylor, Patricia Murray, Steve R. Williams, Jonathan V. M. Weaver, Dave J. Adams and Matthew J. Rosseinsky Affiliations : Anita K. Peacock,a Solène I. Cauët,a Arthur Taylor,b Patricia Murray,b Steve R. Williams,c Jonathan V. M. Weaver,d Dave J. Adamsa and Matthew J. Rosseinskya; a Department of Chemistry, University of Liverpool, Liverpool, UK b Institute of Translational Medicine, University of Liverpool, Liverpool, UK c Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK d Department of Materials and Department of Bioengineering,Imperial College London, London, UK Resume : Polymer-coated inorganic nanoparticles were successfully prepared via grafting of well-defined end-functional polymers prepared by ATRP to iron oxide nanoparticles. With high polymer coverage, the nanoparticles demonstrated good dispersability and colloidal stability in PBS, did not elicit any obvious toxic effects, demonstrated high T2 relaxivity and were readily taken up by stem-cells confirming their potential for biological applications in general and cell-labelling in particular. 16:00 Preparation and characterization of microemulsions containing isopropyl myristate and water with different surfactants as system release of antimicrobial agents Authors : Carolina Carnicel, Mauro A. da Silva, Angélica J. Silva, Josmary R. Silva, Nara C. de Souza, Paula C. S. Souto Affiliations : Grupo de Materiais Nanoestruturados, Universidade Federal de Mato Grosso, Barra do Garças, MT, Brazil Resume : Microemulsions are dispersions of oil and water stabilized by surfactants and co-surfactants. These systems are defined as thermodynamically stable, isotropic, optically clear, and with low viscosity. Microemulsions have applications in drug delivery because they improve the drug absorption and are, in many cases, more efficient than other methods of release. In this study, microemulsion systems were obtained from a topical formulation containing fluconazole. Pseudoternary phase diagrams were used for characterization of the microemulsion. The aim of this work was to prepare and characterize different compositions of microemulsions using water as the aqueous phase, isopropyl myristate as oil phase. Tween 20, Tween 80, and Span 80 were used as surfactants as well as ethyl alcohol as co-surfactant. For each diagram, we have prepared 36 samples, which were visually classified into liquid microemulsion, gel microemulsion, liquid emulsion, gel emulsion, and phase separation. The samples classified as microemulsion and approved in the stability test were characterized using atomic force microscopy (AFM), UV-visible spectroscopy, conductivity and determination of the refractive index. 16:00 Doped Ferrite Nanoparticles For Magnetic Hyperthermia Authors : Aans S Butt [a,b,c], Nguyen T. K. Thanh [a,b], Shinya Maenosono [c]. Affiliations : [a] Department of Chemistry, University College London, Gordon Street, London, WC1H OAJ, U.K [b]the Davy-Faraday Research Laboratory, The Royal Institution of Great Britain, 21 Albemarle Street, London W1S 4BS UK. [c]school of Materials Science, Japan Advanced Institute of Science and Technology, Japan. Resume : The use of hyperthermia in medicine has evolved since its discovery; techniques such as whole body, local and regional hyperthermia have shown excellent results when used in combination with chemotherapy and radiotherapy[1]. Many of these techniques however are too invasive and lack specific targeting of cancerous cells thus leading to side effects. Recently the development of magnetic nanoparticles (MNP) has shown great potential in tackling the problems that have plagued traditional thermotherapy techniques. MNP have been shown to provide focused and targeted heating of malignant cancer cells, while reducing heat exposure in healthy tissue[2]. MNP have also successfully demonstrated their use as drug carriers when combined with hyperthermia [3]. Iron Oxide based MNP have been the choice material for use in magnetic hyperthermia due to their biocompatibility and magnetic properties. This study will 38 39 40

22 sur 25 06/05/2013 09:29 focus on Gd doped-ferrite nanoparticles, synthesised via co-precipitation method in an attempt to produce monodisperse superparamagnetic nanoparticles with a high specific absorption rates (SAR). The structural and magnetic properties of these particles are also studied as are the effects of varying reaction conditions. 1.Zhao, C., Dai, C. & Chen, X. International Journal of Hyperthermia 28, 735?741 (2012). 2.Ahmad, M. Z. et al.. Expert opinion on drug delivery 7, 927?42 (2010). 3.Wahajuddin & Arora, S. International journal of nanomedicine 7, 3445?71 (2012). 16:00 Novel Raspberry Textured Organosilica Nanoparticles for Protein Immobilization and Delivery Authors : Sai P Maddala, Alice Sullivan Affiliations : School of Biological and Chemical Sciences, Queen Mary University of London, E1 4NS Resume : The use of nanoparticle substrates for protein immobilization has potential for application in the fields of drug delivery [1] but is relatively little explored. We have discovered that raspberry textured organomodified silica nanoparticles (70-90 nm) can be synthesized using an organosilanephosphonate group as surface modifier. Two types of phosphonate functionalized nanoparticles, phosphonate monoester (NP_PME) and phosphonic acid (NP_PA) were produced. Large average pore sizes (~12nm) could be achieved as a consequence of the organosilane precursor behaving as a structure directing agent at low base and low surfactant concentration. Other phosphonate esters were explored but did not give the large pore texture. The particles were characterized using porosimetry, TEM, SEM, 31P, 29Si NMR and TGA. The application of these particles as protein immobilization agents was studied using BSA as the model protein. High BSA loadings of 27 and 52 wt % for NP_PME and NP_PA were achieved within a few minutes of exposure. The protein loading was influenced by the phosphonate loading, available surface area and pore size. The BSA loaded nanoparticles were characterized by FTIR, DLS, TEM, SEM, SDS-PAGE and Circular dichroism (CD). The protein adsorbed on the NP_PA retained its secondary structure. We envisage that these particles could have great potential in the areas of enzyme immobilization and protein delivery. [1]. V. S. Y. Lin et al., J. Am. Chem. Soc. 2007, 129, 8845-8849 16:00 Tissue Distribution and Excretion of Silica Nanoparticles in Rats Authors : Hee-Jeong Peak, Hae-Eun Chung, Jeong-A Lee, Mi-Kyung Kim, Youn-Joung Lee, and Soo-Jin Choi Affiliations : Department of Food Science and Technology, Seoul Women s University Resume : Silica (SiO2) nanoparticles have great potential for a wide range of biological and medical applications due to their low toxicity and easy surface modification property. However, despite their wide application in various fields, toxicological effects of silica nanoparticles on human health have not been completely determined yet. Some researches reported on the potential toxicity of silica nanoparticles in vitro and in vivo, but their kinetic behaviors at the systemic level still remain to be elucidated, which is important to understand and predict their possible harmful effects after long-term exposure. In this study, therefore, tissue distribution and excretion profiles of two-different sized silica nanoparticles (20 and 100 nm) were evaluated in male and female rats, respectively, after single-dose oral administration. Quantitative analysis of silica in biological samples was performed using lithium metaborate fusion, followed by molybdenum blue spectrophotometric method. The results showed that small amount of silica nanoparticles were absorbed, while most of them were excreted via the feces. It seems that the liver and kidney are possible target organs for accumulation and toxicity. No significant effects of particle size or gender on biodistribution were found, while larger-sized particles excreted more slowly than small-sized. These findings will provide critical information to predict toxicity potential of silica nanoparticles after long-time exposure. 16:00 Homogeneous hybrid of transition metal hydroxide nanoparticles and biopolymer with transparency and mechanical flexibility Authors : Gyeong-Hyeon Gwak1, Won-Jae Lee2, Seung-Min Paek2*, Jae-Min Oh1* Affiliations : 1Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Gangwondo, 220-710, Korea; 2Department of Chemistry, Kyungpook National University, Taegu 702-701, Korea Resume : We have prepared homogeneous hybrid which consists of transition metal hydroxide nanoparticles and biopolymer via in situ hybridization through electrophoretic method. A cuboid lump of agarose hydrogel was prepared with aqueous Tris-HCl buffer (ph7.4) solution in 1% concentration as a biopolymer framework. Both Ni2+/Ga3+ and OH-/CO32- mixed aqueous solution were prepared and located in a electrophoresis kit separated by the agarose cuboid. By 42 43 44

23 sur 25 06/05/2013 09:29 applying appropriate electrical potential at each side, the cations and anions were forced into the hydrogel resulting in the in situ hybridization of nanoparticles in the biopolymer framework. According to the X-ray diffraction and X-ray absorption spectra, the crystal structure of nanoparticles in the biopolymer was identified as hydrotalcite-like structure with estimated chemical formula of Ni5Ga(OH)12(CO3)0.5. For comparative study, we also prepared the mixed composite by simply mixing molten agarose and equivalent amount of metal hydroxide nanoparticles which were synthesized following conventional method. The scanning electron microscopy showed homogeneous distribution of nanoparticles in the electrophoretically prepared hybrid compared to the simple mixture. According to solid ultraviolet visible spectroscopy and simple mechanical test, we confirmed that the hybrid possesses high transparency and mechanical flexibility compared to the simple mixture which is opaque and fragile. 16:00 Synthesis of superparamagnetic clusters with controlled heteroagglomeration of the nanoparticles in aqueous suspensions Authors : Peter Dušak, Slavko Kralj, Alenka Mertelj, Darko Makovec* Affiliations : Jožef Stefan Institute, Jamova 39, Ljubljana, 1000, Slovenia Resume : Magnetic nanoparticles (NPs) are promising materials for applications in biomedicine, because of their ability to be guided or separated with an external magnetic field. To disperse the magnetic particles, it is beneficial if they are small enough to be in a superparamagnetic state, which is usually below 20 nm. On the other hand, the force acting on a magnetic particle in a magnetic field gradient is proportional to the particle s volume. It appears, in practice, that the individual superparamagnetic NPs are usually just too small to be effectively manipulated. A possible solution for successful manipulation is the use of clusters of superparamagnetic NPs with sizes around 80 nm. In this work, the controlled heteroagglomeration (self-assembly) of superparamagnetic maghemite NPs in their aqueous suspensions was used to prepare the clusters. The surfaces of the NPs were specifically functionalized, i.e., the silane molecules with amino or with carboxyl terminal functional groups were grafted onto their surfaces. Finally, the NPs were heteroagglomerated in their aqueous suspensions due to the electrostatic attractions between the NPs displaying opposite surface charges, or due to chemical interactions achieved through the covalent bonding between the activated surface carboxyl and amino groups, or by using different cross-linkers. 16:00 Coordination multifunctional nanoparticles for theranostics Authors : Fernando Novio (1), Julia Lorenzo (2), Laura Amorin (3), Jordi Hernando (3), Daniel Ruiz-Molina (1). Affiliations : (1) Centro de Investigación en Nanociencia y Nanotecnología (CSIC), Campus UAB, 08193 Cerdanyola del Vallés (Spain); (2) Unitat d Enginyeria de Proteïnes i Proteòmica Institut de Biotecnologia i Biomedicina Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallés (Spain); (3) Departamento de Química. Universidad Autònoma de Barcelona, 08193 Cerdanyola del Vallés (Spain) Resume : Coordination polymers are a fascinating family of superstructures with genuine and highly tailorable properties created from supramolecular assembly of metal ions and organic ligands.[1] Our research group has focused in the systesis of nanoscale coordination polymeric particles (CPPs) with medical applications. These nanoobjects are able to encapsulate a wide variety of sustaces (drugs, metal nanoparticles, quantum dots, etc ),[2] and act as smart response materials.[3,4] In a further step towards their use in theranostics applications, herein we report the functionalización of the nanoparticles surface with different reactive groups, among them, fluoresceine that allows the particles to be followed along the cell internalization process or polyethyleneglycol derivates for their allowing to build new elegant biocompatible multifunctional platforms with interesting applications in medicine for drug delivery, bioimaging or targeting directionality for specific recognition.[5,6] The preliminary results indicate that these new nanosystems open a new wide variety of possibilities to be used in therapy and diagnosis. Refs. 1. I. Imaz, D. Ruiz-Molina et al. Angew. Chem. Int. Ed. 48, 2325 (2009); 2. I. Imaz, D. Ruiz-Molina et al. Angew. Chem. Int. Ed., 47, 1857, (2008); 3. I. Imaz, D. Ruiz-Molina et al. Chem. Commun., 46, 4737 (2010); 4. F. Novio, D. Ruiz-Molina et al. Coord. Chem. Rev. submitted; 5. F. Novio, D. Ruiz-Molina et al. Angew. Chem. Int. Ed. Engl. submitted. 16:00 Synthesis and SERS study of bioconjugated silver nanoparticles. Authors : S. Reymond-Laruinaz, L. Saviot, M. C. Marco de Lucas Affiliations : Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), UMR 6303 CNRS-Université de Bourgogne, 9 Av. A. Savary, BP 47 870, F-21078 DIJON Cedex, FRANCE Resume : Bioconjugated synthesis by proteins enables the design of biocompatible metal nanoparticles [1]. Such nanoparticles are promising candidates for many 45 46 47

24 sur 25 06/05/2013 09:29 biomedical applications. Their direct silver/protein interface also makes them good models for studying protein detection by Surface Enhanced Raman Scattering (SERS). In this work, silver nanoparticles were synthesized in the presence of several proteins (bovine serum albumin (BSA), hemoglobin, lysozyme and cytochrome C). Scanning electron microscopy (SEM) images show populations of nanoparticles stabilized by the proteins used during synthesis. The study of these bioconjugated particles by Raman spectroscopy was performed. The SERS effect allowed recording the spectra of the proteins despite the low concentration used during synthesis (1mg/mL). The differences between the spectrum of the protein and the spectrum of the bioconjugated nanoparticle give informations on the protein/nanoparticle interactions and structural changes of the protein. The goal of this study is to provide a better understanding of the spectral fingerprint of different proteins in the specific conditions required for obtaining SERS enhancement. The results will contribute to understanding the behavior of nanoparticles in a biological environment [2, 3] and results can also provide information on the mechanisms of synthesis by biomineralization. [1] Poonam Khullar et al., J. Phys. Chem. C, 2012, 116 (15), pp 8834 884 [2] M. Lundqvist, et al., AC 16:00 Size dependent cellular behavior of layered double hydroxide nanomaterials in human cancer cell lines Authors : Kyoung-Min Kim1, Byung Chul Jung2, Yoon Suk Kim2*, and Jae-Min Oh1* Affiliations : 1Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Gangwondo 220-710, Korea; 2Department of biomedical laboratory science, College of Health Sciences, Yonsei University, Wonju, Gangwondo 220-710, Korea Resume : We have studied the cellular interaction of layered double hydroxides (LDH) nanomaterials with human cancer cell lines. In order to investigate the particle size effect, we prepared three LDH samples with different particle sizes. Both hydrothermal treatment followed by coprecipitation and controlled urea hydrolysis methods were employed to control the particle size. The scanning electron (SEM) and atomic force microscopy (AFM) showed that the primary particle sizes of three LDH nanomaterials are ~ 20, ~ 200, and ~ 2000 nm, respectively. The dynamic light scattering patterns of LDH nanomaterials were analyzed in several media such as deionized water and phosphate buffered saline (PBS), slight agglomerates being observed in PBS. Two human cancer cells, A549 (adenocarcinomic human alveolar basal epithelial cell) and AGS (human gastric adenocarcinoma cell) were chosen for cellular study and three LDH nanomaterials suspended in PBS were administered to both cell lines. The time and concentration dependent LDH-cell interaction were monitored with microscopies. According to SEM and AFM, the LDH nanomaterials began to interact with the cells around the periphery in low concentration and early time, and then gradually cover the upper cellular surface according to the increasing concentration and incubation time. 16:00 Application of Fe-based nanoparticles produced by solar PVD as magnetic hyperthermia agents Authors : K. Simeonidis (1), M. Tziomaki (1), M. Angelakeris (2), T. Samaras (2), O. Kalogirou (2), G. Vourlias (2), N. Andritsos (1), C. Martinez-Boubeta (3), L. Balcells (4), C. Monty (5) Affiliations : (1) Department of Mechanical Engineering, School of Engineering, University of Thessaly, 38334 Volos, Greece; (2) Department of Physics, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece; (3) Departament d'electrònica, MIND-IN2UB, Universitat de Barcelona, 08028 Barcelona, Spain; (4) ICMAB, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; (5) Procédés, Matériaux et Energie Solaire, CNRS, 66120 Font-Romeu, France Resume : This work attempts to evaluate the heating response at AC magnetic field of spherical Fe-based nanoparticles prepared by solar physical vapor deposition (SPVD) under the prism of their composition, size and magnetic properties. More specifically, the studied systems (40-70 nm) were grown by 49 evaporating Fe and Fe3O4. The target-material (cold-pressed Fe3O4 or Fe powder) was placed onto a water-cooled holder in the center of a glass vacuum chamber and transferred to the focus of the sun beam concentrator. Particles were collected in a cold finger (nanoporous ceramic filter). Due to their improved crystallinity and magnetic anisotropy, Fe3O4 nanoparticles lying in the magnetic monodomain region present enhanced specific absorption rates (maximum SAR=0.9 kw/g at 765 khz) at variable frequency fields. Their increased heating efficiency compared to zero-valent Fe nanoparticles may be attributed to the activation of magnetic hysteresis losses mechanism in combination to their chemical stability against surface oxidation. This work was implemented within the framework of Action «Supporting Postdoctoral Researchers» of Operational Program Education and Lifelong Learning (Action s Beneficiary: GSRT), and is co-financed by ESF and Greek 48

25 sur 25 06/05/2013 09:29 State. Financial support by the Access to Research Infrastructures activity in the 7th Framework Programme of the EU (SFERA Grant Agreement n. 228296) is gratefully acknowledged. C. M. Boubeta thanks the Ramón y Cajal Spanish program. 16:00 Remote control of reaction-diffusion processes in compartmentalized microparticles Authors : M. Ullrich, P. Haufová, M. Singh, O. Kašpar, J. Hanuš, M. Štěrbák, F. Štěpánek Affiliations : Department of Chemical Engineering, Institute of Chemical Technology Prague, Technicka 5, 166 28 Prague 6, Czech Republic, tel. +420 220 443 236, e-mail: frantisek.stepanek@vscht.cz Resume : Inherently unstable or highly reactive molecules are potentially attractive drug candidates they can offer high potency with no or low side effects, and avoid the risk of drug resistance. However, conventional drug delivery technologies are not suitable for such molecules. In natural systems, such molecules are formed by an enzymatic reaction in situ only when needed. The aim of the present work is to mimic this behavior and produce micro-particles for controlled delivery applications, consisting of reservoirs filled with precursor molecules separated from an enzyme. The precursor and the enzyme react after an external stimulus and a reaction product can diffuse out of the particles. We will present composite microparticles where liposomes play the role of the storage compartments and iron oxide nanoparticles perform the role of local stimuliresponsive heat sources. Both components are embedded within hydrogel microparticles produced by the ink-jet method. An enzyme (laccase) is also present in the hydrogel. The beads are coated by a self-assembled silica layer that provides mechanical and chemical stability and allows functionalization for specific adhesion. The enzymatic oxidation of ABTS will be used as a model reaction and its progress monitored spectrometrically. The influence of iron oxide nanoparticle concentration, enzyme concentration, and hydrogel density on the kinetics of coupled reactiondiffusion processes from the composite particles will be investigated. 50 Back European Materials Research Society 23 Rue du Loess - BP 20-67037 Strasbourg Cedex 02 - France - Phone:+33-(0)3 88 10 63 72 - Fax:+33-(0)3 88 10 62 93 - emrs@emrsstrasbourg.com

1 sur 9 06/05/2013 09:30 PROGRAM VIEW : 2013 Spring MY PROGRAM : 2013 Spring Symposium : U Design of multifunctional nano-objects for biomedical applications 27 May 2013 28 May 2013 29 May 2013 30 May 2013 31 May 2013 hide a start at Subject Num. Nanoparticle design 1 : F. Herranz - P. Morales 08:30 Synthesis and optical trapping of individual thermo-responsive beads with colloidal quantum dots and Au nanoparticles Authors : Silvia Hormeno (1), Holger Lange (2), J. Ricardo Arias-Gonzalez (3) and Beatriz H. Juarez(4) Affiliations : (1) Instituto de Microelectronica de Madrid, CSIC, Isaac Newton 8, 28760, Madrid, Spain; (2) Columbia University, Depts of Physics and Electrical Engineering, 530 West 120th Street New York, NY 10027, United States; (3) IMDEA Nanoscience, Faraday 9, 28049, Madrid, Spain; (4) Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain. Resume : In this work a brief description of the synthesis of thermoresponsive microspheres (poly(n-isopropylacrylamide, pnipam) decorated with water soluble CdSe/CdS core-shell quantum dots (QDs) and/or Au nanoparticles along with cell culture studies will be given [1]. These systems combine the ability for thermal sensing (due to the properties of pnipam systems), and labeling (due to the QDs), representing very interesting platforms for the design of thermal sensors in 4 1 biological studies. The combination of pnipam micro- and nanospheres with Au nanoparticles allows controllably and reversibly tuning the optical properties of the nanoparticles. [2] The ability to trap and manipulate those platforms along with the possibility to immobilize cells or organelles in fixed positions opens the way to carry out imaging studies. We have studied the hydrodynamic size and optical response of individual spheres composed of both colloidal quantum dots and Au nanoparticles by optical tweezers. [3] From the trapping experiments we show that while moderate shrinkage is observed for bare pnipam beads, severe shrinkage is observed for pnipam/au ones due to the extra heating induced by the presence of a surface ensemble of Au NPs. The presence of CdSe/CdS QDS on the pnipam beads reduces the local heating of water in the polymeric network leading to higher sizes. [1] Journal of Materials Chemistry 20, 1367?1374, (2010) [2] Langmuir, 28, 24, 8862?8866, (2012) [3] Nano Letters, 11, 11, 4742?4747, (2011) 09:00 Tailoring Au/LDHs nanoarchitectures for controlled delivery of gold nanoparticles Authors : Gabriela Carja1, Magda Puscasu1, Dragos Mardare1, Kiyoshi Okada2, Affiliations : 1 Department of Chemical Engineering, Faculty of Chemical Engineering and Environmental Protection, Technical University Gh. Asachi of Iasi, Bd. Mangeron no.71, Iasi 700554, Romania; 2 Materials and Structures Laboratory, Tokyo Institute of Technology, 4259, Nagatsuta, Midori, Yokohama, Tokyo, 226-8503, Japan corresponding author: e-mail: carja@uaic.ro Resume : Nanosized gold has size-dependent optical and phototermal properties that are of high interest for applications in targeted cancer detection and thermotherapy. The stability and controlled delivery of gold nanoparticles are key-variables in tailoring nanogold for biomedical applications. We present here nanoparticles of gold - layered double hydroxides (Au/LDHs) as new nanoarchitectures able to incorporate, storage and controlled release nanoparticles of gold. Layered double hydroxides (LDHs) are a class of anionic clays. They have attracted great attention in many technological important fields, such as nanomedicine and nanotechnology, due to their interesting properties in anion exchangeability, adsorption flexibility and biocompatibility. The fabrication of Au/LDHs is simple and cost effective; it is based on the formation of nanoparticles of Au on the surface of the anionic clay during the structural reconstruction process of the layered clay matrix. Powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), high resolution transmission electron microscopy (TEM) and UV-Vis spectrometry (UV-Vis) measurements were used to investigate the structure, composition and size-dependent optical characteristics of the gold-clay 4 2

2 sur 9 06/05/2013 09:30 assemblies. Results show that the release profiles of the gold nanoparticles from the clay matrices is influenced by the anionic clay composition. The antimicrobial properties of Au/MgAlLDH and Au/ZnAlLDH against gram-positive bacteria and gram-negative bacteria are also studied. 09:15 Investigation on thermally activated gold nanoparticles using Molecular Dynamics Authors : J.Soussi, S.Volz, Y.Chalopin Affiliations : Laboratoire EM2C, Ecole Centrale Paris Resume : We propose a Molecular Dynamics study of thermally activated agglomeration of gold nanoparticles covered by polymers in water. Nanoscale heat transfer and contact resistances at the gold/water and gold/polymer interfaces have been computed and the phase transition of the polymers allowing the agglomeration has been investigated. 09:30 Highly versatile approach for the preparation of bioactive multifunctional nanotubes and nanowires Authors : Cécile J. Roy, Deepak Kalaskar, Jessem Landoulsi, Christine Dupont-Gillain, Alain M. Jonas, Sophie Demoustier-Champagne Affiliations : Université catholique de Louvain (UCL), Institut de la Matière Condensée et des Nanosciences (IMCN), Bio- and Soft Matter (BSMA), Croix du Sud, 1, Louvain-la-Neuve, Belgium. E-mail: sophie.demoustier@uclouvain.be Resume : Nanorods and nanotubes consisting of segments of different materials that can either perform specific functions or selectively interact with specific ligands have emerged as a new class of advanced one-dimensional nanomaterials. In this context, we are developing a versatile way of synthesizing and assembling hybrid multisegmented functional nanostructures of various degree of complexity. We successfully combined the membrane-templating method with electrodeposition and layer-by-layer (LbL) assembly to create various multisegmented nanostructures composed of metals, polymers, synthetic and biological polyelectrolytes, and colloids. The electrochemical approach offers the control over the architectural parameters of the resulting structures (in particular the segment length and morphology) while the LbL adsorption technique permits to integrate non-conducting materials, including biomacromolecules (such as DNA, polypeptides, polysaccharides and proteins), within the nanostructures. A supplementary degree of complexity can be reached by capping or loading the LbL nanotubes with colloidal particles. The ability to easily generate such hybrid anisotropic nanoparticles with spatially resolved chemical, physical, and biochemical functionalities is a boon for the synthesis of nanostructures, which is of tremendous importance for electronic, catalysis, sensing, drug delivery, and modern biomedical and biotechnological applications. In this communication, we will focus on our most recent results concerning the design and elaboration of functional nano-objects through this methodology with a special highlight onto the synthesis and properties of biomacromolecule-based nanotubes. 09:45 Synthesis and thermo-responsive properties of magnetic nanoparticles coated with pluronic /PEG polymers Authors : K. Hervé Aubert, M. Chiper, A. Augé, J.F. Fouquenet, I. Chourpa Affiliations : K. Hervé Aubert, A. Augé, J.F. Fouquenet, I. Chourpa : Nanomédicaments et Nanosondes, EA 6295, Université François Rabelais de Tours, 31 avenue Monge, 37200 Tours ; M. Chiper : Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, 67401 Illkirch Cedex, France. Resume : Superparamagnetic iron oxides nanoparticles (SPIONs) are known to be an attractive platform as contrast agents for magnetic resonance imaging and as drug carriers. Recently, we reported a one-pot synthesis protocol for highly efficient and stable covalent binding of both the fluorescent drug doxorubicin and the biocompatible polymer poly-(ethyleneglycol) modified with folates to the surface of SPIONs. We obtained a stable colloidal solution where folate to the surface of nanoparticles can efficiently target the site of tumor. Nevertheless, the PEG shell seems to reduce the access of cellular enzymes to the drug-particle linkage and thus limits and/or delays the anticancer effect. Thus, to stimulate the drug release, we realized the combination of SPIONs with thermo-responsive block copolymers type pluronic, composed of one PPO block connected to two PEO blocks. The concept consists to incorporate drug into the hydrophobic compartment of polymers and use thermo-responsive properties of polymers to release drug. In order to prevent instability of suspension and obtain critical temperature near 40 C, we choose to prepare nanovectors with a mixture between two polymers: thermoresponsive pluronic and hydrophilic PEG. So, we produced, in a one-pot synthesis, iron oxide nanoparticles coated with pluronic F68, FA modified pluronic F68 and PEG. The colloidal solution was characterized with atomic absorption, FT-IR spectroscopy, photon correlation spectroscopy used for hydrodynamic diameter and 4 3 4 4 4 5

3 sur 9 06/05/2013 09:30 zeta potential measurements. Doxorubicin and the hydrophobic dye are encapsulated into nanovectors and release profiles of molecules from the nanoparticles were studied as functions of temperature via fluorescence measurements. 10:00 Coffee break Nanoparticles for therapy : B. Hernandez Juarez - C. Billotey 10:30 Nanoparticles for therapy of Alzheimer disease Authors : Masserini M., Re F. Affiliations : Department of Health Sciences, University Milano Bicocca Resume : Several clues suggest that the overproduction and subsequent accumulation of β-amyloid (Aβ), a proteolytic fragment of the membraneassociated amyloid precursor protein (APP), plays a central role in AD. NAD project (large cooperative; 19 partners, funded by the E.C., FP72007-2013, G.A. n? 212043) is aiming to the therapy and diagnosis, even combined, of AD, by creating different multiple-functionalized nanoparticles, able to bind, detect and remove Aβ from the brain and from the blood. We have realized different types of NPs (liposomes, SLN) specifically functionalized with acidic lipids to bind Aβ with high affinity. These NP proved their potential to be used for the therapy of AD by preventing, in vitro, Aβ aggregation, neurotoxicity of Aβ peptide, and Aβ-induced Tau phosphorylation. Further functionalizations for crossing the BBB have been performed and tested on a BBB in vitro transwell model utilizing brain capillary endothelial cells, human (hcmec/d3) or murine (RBE4). Double functionalization (both for binding Abeta and for crossing the BBB) enhances NP cell uptake and transport across the BBB model without affecting the affinity for Abeta. Experiments in vivo carried out on animal models of Alzheimer disease (single and double TG mice) show that after treatment with single or double-functionalized NP, the levels of β-amyloid circulating in blood and β-amyloid oligomers in brain have a tendency to decrease. Finally, parallel experiments show that treatment of TG mice with double-functionalized NP can decrease the content of Abeta in brain. Taken all together, these results open new possibilities for the treatment of Alzheimer Disease. 11:00 High loaded Lopinavir and Ritonavir combination nanoparticles for HAART therapy against HIV Authors : Dr Marco Giardiello, Dr Tom O McDonald, Dr Philip Martin, Dr Niell Liptrott, Dr Darren Smith, Prof Andrew Owen, Prof Steve Rannard Affiliations : Department of Chemistry, University of Liverpool, UK; Department of Molecular & Clinical Pharmacology, University of Liverpool, UK Resume : To suppress the proliferation of HIV a strategy known as Highly Active Antiretroviral Therapy (HAART) is employed, relying on the administration of antiretroviral drugs, taken in combination. Such drugs, however, are often toxic, expensive and highly water insoluble which gives rise to poor bioavailability. To overcome such issues drugs are dosed in high quantities which is far from ideal due to their toxic nature. Herein, a strategy to develop combination nanoparticles of the protease inhibitor Lopinavir (LPV) and the cytochrome P450 3A4 inhibitor Ritonavir (RTV) is presented. These drugs are currently used in HAART therapy in a 4:1 LPV:RTV combination. A generic strategy has been employed for producing organic nanoparticle dispersions via a combination of modified emulsion templating and freeze-drying. This produces amorphous dry powder composites which are highly stable and form nano-dispersions upon simple addition of water, which show properties similar to those of aqueous molecular solutions and as such raise bio-availability. The technique involves the preparation of an oil in water (O/W) emulsion in which the organic compounds are present in the volatile organic oil phase while the aqueous phase contains a mixture of stabilisers (PVA/TPGS). A 70% drug loaded 4:1 LPV:RTV particle has been developed (20 % PVA and 10 % TPGS), which shows low cytotoxicity, high cellular accumulation and considerably enhanced bioavailability in vivo. 11:15 Designing NANOBOTS to fight Cancer Authors : Víctor F. Puntes Affiliations : Catalan Institute of Nanotechnology (ICN) Resume : How to make a multifunctional nanoparticle that meets all of the nanoscale properties that are useful in the fight against cancer. These are: accompanying the drug, passivation during travel, contrast agent, hyperthermia 5 1 5 2 5 3

4 sur 9 06/05/2013 09:30 agent (magnetic and terahertz-nir), proton pump, anti-inflammation (or immunoexacerbation), substrate for the attachment of multiple drugs and multiple ligands including antibodies, haptens and nucleotides. So one has combined chemotherapy and radiation therapy enhancers and boosters in the same nanoparticle, what allow better theranostics and monitoring of disease progression / therapy (if not directly analyzing tissues if nanoparticles can be analyzed as witnesses to what is happening in the tissue). The result is a multifunctional nanoparticle optimized in size and surface condition (interaction with proteins/protein corona) for optimal biodistribution and EPR. The result, with inorganic nanoparticles is one which has a gold hollow interior loaded with drug (in a second step coated with a thermosensitive polymer to remotely control drug release) on which nanoscale domains have grown iron oxide and cerium oxide which have functionalized molecules and drugs desired directors. This nanoparticle are responsive to external radiation, absorbing high-energy photons in radio therapy, radio frequency waves via its magnetic moment or photons in the near infrared due to the surface plasmon resonance. 11:30 Rapid Generation of Solid Drug Nanoparticles for HIV Nanotherapies Authors : Steve Rannard, Andrew Owen, Tom McDonald, Marco Giardiello, Phillip Martin, Darren Smith, Neill Liptrot, Alison Foster, Ania Latusek, Lynn Power Affiliations : University of Liverpool - Steve Rannard, Andrew Owen, Tom McDonald, Marco Giardiello, Phillip Martin, Darren Smith, Neill Liptrot; IOTA NanoSolutions Ltd - Alison Foster, Ania Latusek, Lynn Power Resume : Antiretrovial drugs are critical to the control of HIV globally. Currently there are no clinically available nanomedicines to generate new benefits for HIV patients (current estimates suggest >35million adults and children worldwide) and candidate therapies must be orally available as chronic dosing via injection is not acceptable to patients. Oral dosage forms for nanomedicines have predominantly been generated using nanomilling to produce solid drug nanoparticles (SDNs). Here we present a rapid emulsion-templating freeze-drying approach (generating SDNs from solutions of drug), a method for identifying appropriate excipients for stable drug nanodispersions and a protocol for quickly determining candidate nanomedicines. An example using Efavirenz, the front-line therapy for new HIV cases globally, will be used to explain the process, including detailed biological studies (cytotoxicity, accumulation, transport) in cell lines and primary cells, virology, immunology, in vivo bioavailability and progress towards human trials of the world's first orally dosed antiretroviral nanomedicine. 11:45 Framework for developing radio- chemo-combination cancer therapies involving bioactive (functionalized) nanoparticles Authors : 1. F.J.Currell, 2. M.E.Hubbard, 3. R.J.W.Lambert, 4.K.Polizzi, 5.C.Shankland, Affiliations : 1. School of Maths and Physics, Queen s University, Belfast, BT7 1NN 2. School of Computing, University of Leeds, LS2 9JT, UK 3. Cranfield Health, Cranfield University, MK45 4DT, UK 4. Centre for Synthetic Biology and Innovation, Imperial College London, SW7 2AZ, UK 5. School of Natural Sciences, University of Stirling, FK9 4LA, UK Resume : Chemo-radiation therapy whereby a chemical agent and radiation are used together represents an attractive approach to treating cancer. To be effective the chemical agent should be delivered preferentially to the tumour, which is then targeted with radiation therapy. If the chemical agent and the radiation act synergistically the result is an increased therapeutic window, something highly desirable in cancer treatment where a major challenge is the very narrow therapeutic windows found for either radiotherapy or chemotherapy alone. Functionalised nanoparticles represent particularly attractive chemical agents in this context. They can be used to traffic high concentrations of drug agents to the tumour. Furthermore, their action can be triggered by the radiation. If they have a heavy atom (e.g. gold) in the core then they have a proven synergistic interaction. However the rational design of functionalized nanoparticles optimized for this application is challenging, requiring a multi-disciplinary skill set. In a 5-centre EPSRC-supported project we are developing a computational/mathematical framework capturing both local treatment effects and whole-body effects. Informed by a small set of characterisation experiments, it will predict the tissue distribution and efficacy of a given nanoparticle and perform in-silico trials, thereby providing a paradigm shift in the development of functional bioactive nano-objects in the context of radio-chemo combination therapy. 5 4 5 5 12:00 Lunch

5 sur 9 06/05/2013 09:30 Magnetic nanoparticles : M. Masserini - S. Begin 13:30 Therapeutic performance of PEG-PAMAM dendrimers functionalized magnetic nanoparticles towards cervical cancer Authors : Saumya Nigam1, Qizhi Chen1,2, D. Bahadur*1,3 Affiliations : 1 IITB-Monash Research Academy, IIT Bombay, Mumbai 400076, India 2 Department of Materials Engineering, Monash University, Clayton, Victoria, 3800, Australia 3 Department of Metallurgical Engineering & Material Science, IIT Bombay, Powai, Mumbai 400076, India Resume : Superparamagnetic iron oxide nanoparticles have recently received a great deal of attention due to their potential applications in the field of medical biotechnology. They have been thoroughly investigated for their prospective use in biomedicine as drug delivery vectors, MR imaging contrast agents, and magnetic drug targeting and hyperthermia treatment of cancer. Our objective is to fabricate smart magnetic nanoparticles (MNPs) by soft chemical route for possible delivery vectors to cancer cells. A single-step facile approach for fabrication of glutamic acid functionalized aqueous colloidal Fe3O4 (IO-Glu) nanoparticles using co-precipitation method was employed. Polyethylene glycol modified-polyamidoamine (PEG-PAMAM) dendrimers (generations 3, 5 ad 6) were utilized to modify the nanoparticles surface to anchor the cargo (therapeutic) molecules. The nanoparticles were characterized by X-Ray diffraction (XRD), magnetization measurements (VSM), specific absorption rate (SAR) and micrograph (TEM) studies. The XRD pattern revealed the formation of single-phase Fe3O4 inverse spinel structure with lattice constant of 8.4 A while the TEM micrographs confirmed the size of the nanoparticles to be 10-15 nm (( 10%). The conjugation of PEG-PAMAM dendrimers to these nanoparticles does not affect their crystallinity while their size increased to an average of 24 (G3), 33.7 (G5) and 38.3 (G6) nm. The VSM measurements of field dependent magnetization (M vs. H) of the magnetic nanoparticles (IO-Glu) showed a maximum magnetization of 57 emu/g at 20 koe for room temperature measurements. Conjugation of PEG-PAMAM dendrimers to these nanoparticles exhibited a reduction in their saturation magnetization lowering to the values of 48.2 (G3), 37.2 (G5) and 32.9 (G6) emu/g. Time-dependent calorimetric measurements (SAR) of IO-Glu suspension evaluated its heating efficacy as additional functionality which is an essential requirement of the hyperthermia treatment of cancer and resulted in the values of 35.62, 39.47 and 51.43 W/g with an applied field (H) of 7.64, 8.82 and 10.0 ka/m, respectively. The surface functionalization and properties were confirmed from infrared spectroscopy (FTIR), thermal analyses (TGA), and zeta-potential measurements. The functionalization of glutamic acid molecules on the surface of Fe3O4 nanoparticles rendered a positively charged surface with a moderate surface charge of +18.6 mv suggesting the use of COOH groups of the amino acid for attachment to the magnetic nanoparticles rendering the NH2 groups free on the nanoparticle surface and thus resulting in an average stability of the colloidal suspension of MNPs. Whereas, the surface modification by the PEG-PAMAM lowered the surface charge to -20.4 (G3), -23.9 (G5) and -31.7 (G6) mv accounting for the presence of negatively charged PEG molecules on its surface and improving the colloidal stability of the formulations. The system was investigated using Epigallo catechin gallate (EGCG) and doxorubicin hydrochloride (DOX) as exemplary drugs to evaluate its efficiency as delivery system to cancer cells. While DOX is established as a potent anti-cancer drug, recent works have established the anti-cancer properties of the green tea extract making EGCG a potential choice for a new class of chemotherapeutics for cancer. EGCG carries an abundance of OH groups on the surface whereas DOX exhibit the presence of OH, NH2 and C=O groups which facilitate their conjugation with the dendrimer conjugated iron oxide nanoparticles. The results show that the drug molecules are entrapped onto the nanoparticles via the electrostatic interactions with loading efficiencies of 32.7, 51.1 and 56.4 % respectively for EGCG molecules and 86.9, 93.2 and 96.1 % respectively for DOX molecules. The drugs were released in mild acidic environments (stimulus) mimicking the tumors, and the release profiles indicate an incomplete release of EGCG molecules (37.9, 43 and 59.5%) for the period of 24 hours while DOX molecules were released (58.4, 65.4 and 76.3%) within initial 10 hours and attaining a plateau thereby exhibiting a sustained release profile. A dose-dependent investigation of the formulations was performed against cancer cell line of cervical cancer (HeLa) to evaluate their anticancer activity leading to an inhibition of cell proliferation in the cell lines. The results show that the MNPs and dendrimer conjugated magnetic nanoparticles do not hinder the cell growth and no change in cellular morphology was observed, suggesting that the particles and the conjugates are biocompatible at low concentrations of the material; cell proliferation activity as high as 100% is observed. The drug toxicity profiles of EGCG and DOX show inhibition of cell proliferation activity to reduce the cell growth by 40% (EGCG) and 6 1

6 sur 9 06/05/2013 09:30 80% (DOX). The IC50 values of the formulations were calculated by the dose-responsive sigmoidal curve fitting and were found to be 100.3, 79.1 and 50.75 µg/ml (EGCG) and 17.4, 12.9 and 9.25 µg/ml (DOX) of the drug loaded nanoparticles. As the anti-cancer toxicity of the formulations is established, the SAR measurements of these formulations open up their possibilities in their further utilization in a combinatorial therapy involving hyperthermia in addition to the classic chemotherapy. 14:00 Autoclave Syntheses of FePt Nanoparticles with Improved Magnetic properties Authors : Luke A. W. Green, Nguyen T. K. Thanh, Quentin A. Pankhurst Affiliations : University College London, Gower street, London, WC1E 6BT, United Kingdom The Royal Institution of Great Britain, 21 Albemarle Street, London, W1S 4BS, United Kingdom. Resume : We report FePt nanoparticles with increased Fe content and increased magnetic saturation through the use of pressure during synthesis. A comparison of Schlenk line and autoclave syntheses is presented. Selectivity of the monodentate and bidentate bonding between oleic acid and the NPs was achieved by adjusting the precursor amounts. XRD patterns increase in angle 2θ with increased amount of Fe. Nanoparticles exhibit shape factors dependent on the ratio of oleic acid and oleylamine used. Transmission electron microscopy, dynamic light scattering, X-ray diffraction, super-conducting quantum interference device magnetometry, inductively coupled plasma atomic emission spectroscopy, and Fourier transform infra-red spectroscopy analyses are presented and discussed. FePt NPs show potential as alternative magnetic materials for use in biomedicine due to a greater emu.cm3 than clinically approved and commercially available iron oxide derivatives. 14:15 Unexpected non linear weak-field magnetic behavior of ferrite nanoparticles: towards multiparametric immunoassays application Authors : C. de Montferrand1,2, L. Hu3, I. Milosevic2, D. Bonnin4, V. Russier5, A. Brioude3, Y. Lalatonne2,6, L. Motte2 Affiliations : 1.Magnisense, Paris, France; 2.Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS UMR 7244, Bobigny, France; 3.Université Lyon 1, LMI, CNRS UMR 5615, Villeurbanne, France; 4.ESPCI ParisTech UPMC, LPEM, CNRS UMR 8213, Paris, France; 5.ICMPE MCMC, CNRS UMR 7182, Thiais, France; 6.APHP, Service de Médecine Nucléaire, Hosp Avicenne, Bobigny, France Resume : The use of magnetic nanoparticles (MNPs) has grown significantly in the field of bioassays as their physico-chemical properties allow faster assays and can improve sensitivity. Magnisense has developed a unique newly patented instrument, portable, high sensitive and working at room temperature, called MIAplex [1] which measures the non-linear magnetization second derivative at low field (±36 ka.m-1). Depending on size, shape and composition of MNPs, the resulting measurements provide specific magnetic signatures, allowing multiple detection. In a first study we present an in-depth structural and magnetic characterization of γfe2o3 MNPs of variable sizes [2,3]. Relevant parameters (size, polydispersity, magnetic dipolar interactions, surface) are explored in order to correlate the second harmonic signature measured with the MIAplex sensor and the SQUID second derivative. In a second study, the magnetic response of ferrite MNPs differing in their shape is presented [4]. These resulting specific signatures are very promising for the use of the MIAplex technology for the simultaneous detection of biological molecules. [1] Lalatonne Y. J. Magn. Magn. Mater. 2009; 321 (10): 1653. [2] de Montferrand C et al. Analyst 2012; 137: 2304. [3] de Montferrand C et al. Small 2012; 8: 1945. [4] de Montferrand C et al. Acta Biomaterialia, doi 10.1016/j.actbio.2012.11.025 14:30 Aqueous synthesis and coating strategies of uniform large magnetite nanocrystals with high saturation magnetization values Authors : Marzia Marciello,1 Sabino Veintemillas-Verdaguera,1 Manuel Andrés Vergés,2 Carlos J. Serna,1 M. Puerto Morales,1 Affiliations : 1 Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), C/ Sor Juana Inés de la Cruz 3, 28049 Madrid, Spain; 2 Departamento de Química Orgánica e Inorgánica, Universidad de Extremadura, Avda Elvas s/n, 06071 Badajoz (Spain) Resume : Magnetic hyperthermia is an attractive strategy of cancer treatment based on heat generation on tumor site resulting in cancer cell death, presenting fewer side effects compared to chemo- and radiotherapy and that can be used in combination with all conventional therapeutic strategies. Magnetic nanoparticles used for this treatment convert their dissipated magnetic energy into thermal energy able to heat the tumoral cells. Therefore, high saturation magnetization values are important for an effective heating of the particles [1, 2]. In this work we 6 2 6 3 6 4

7 sur 9 06/05/2013 09:30 show the aqueous synthesis of uniform large magnetite nanocrystals (~20nm) with high saturation magnetization values (~80emu/g) [3] and coating strategies specifically adapted to stabilize these large magnetic particles in colloidal suspensions under physiological conditions and at high concentrations (5mg/ml), as those required for intravenous and intratumoral injection (hydrodynamic size of around 200nm). Surface modification of the particles with inorganic and organic biocompatible molecules covalently bound is the critical step not only to avoid aggregation but also to get additional functionalities to bind drugs and to strongly affect cell uptake and biodistribution. References [1] Hilger I., Kaiser W.A., Nanomedicine 7 (9) (2012): 1443-1459 [2] Kumar C.S.S.R., Mohammad F., Adv drug Deliver Rev 63 (2011): 789-808 [3] Vergés M.A., Costo R., Roca A.G., Marco J.F., Goya G.F., Serna C.J., Morales M.P., J Phys D: Appl Phys 41 (2008): 1-10 14:45 Synthesis and magneto-rheological properties of magneto-sensitive bionanocomposites Authors : Laurence Ourry(1), Fayna Mammeri(1), Cecilia Galindo-Gonzales(2), Alain Ponton(2), Souad Ammar(1) Affiliations : (1) ITODYS, UMR CNRS 7086, Université Paris Diderot,Sorbonne Paris Cité, France ; (2) MSC, UMR CNRS 7057, Université Paris Diderot, Sorbonne Paris Cité, France Resume : Recent progresses in Chemistry, Physics and Biology lead to the synthesis of new hybrid materials for medical applications. Biopolymer networks loaded with magnetic nanoparticles are of particular interest because they are hydrophilic, biodegradable and biocompatible with biological molecules, cells and tissues. Theses hydrogels loaded with magnetic nanoparticles exhibit self-assembly morphologies and can form new materials for drug delivery. Maghemite nanoparticles (gamma-fe2o3) were synthesized using the polyol process. We improved the dispersion of nanoparticles in the polymer network by a suitable surface functionalization, using various organic bifonctional ligands: dopamine, aminopropyltriethoxysilane and aminophosphonic acid, changing the nature of the interaction between nanoparticles and ligands, from electrostatic to covalent bonds. These functionalized magnetic nanoparticles are introduced in aqueous solution of sodium alginate, a natural polysaccharide isolated from algae. Preliminary rheological measurements under magnetic field of these nanocomposites were performed for the first time, using a new magnetorheological cell developed at MSC. A very interesting reversible change of the viscoelastic behaviour was observed when a magnetic field was applied. All materials were found to be sensitive to the intensity of the magnetic field. 15:00 Magnetic Polymersomes A Versatile Tool for Targeted Cancer Therapy Authors : Regina Bleul, Raphael Thiermann, Urs Häfeli, Michael Maskos Affiliations : BAM Federal Institute for Materials Research and Testing, Berlin, Germany; BAM Federal Institute for Materials Research and Testing, Berlin, Germany; Pharmaceutical Sciences, UBC, Vancouver, Canada; Institut für Mikrotechnik Mainz IMM, Mainz, Germany Resume : Nanomedicine requires well-engineered and safe nanotransporters, in particular for highly cytotoxic drugs, as they are often applied in cancer therapy. Such drug carriers will allow a more specific and targeted drug delivery to the diseased tissue to improve therapeutic efficacy and reduced adverse side effects. Polymeric vesicles (Pluronic L 121) dual loaded with the anti-cancer drug camptothecin and magnetic nanoparticles (MNP) were prepared continuously using micro mixing technology. Successful incorporation of the MNP was confirmed by TEM imaging and DLS measurements showed a narrow size distribution of the hybrid polymersomes. A high drug loading of camptothecin (100 µg/ml) was reached and the polymersome formulation showed a sustained drug release over several days. Camptothecin polymersomes reduced the cell viability of prostate cancer cells (PC-3) measured after 72 h significantly, while drug-free polymersomes showed no cytotoxic effects. Bombesin, a 14 amino acid peptide, was attached to the polymersome surface. This ligand binds specifically to the GRP-Receptor (Gastrin Releasing Peptide Receptor), which is often overexpressed in tumor cells and therefore a suitable target for cancer treatment. Targeting efficiency was confirmed by flow cytometry and polymersome internalization was visualized by confocal microscopy. Relaxivity measurements to evaluate the potential of magnetic polymersomes as MR contrast agent are in progress. Further biomedical applications of magnetic polymersomes e.g., as tool for hyperthermia treatment, magnetic drug release triggering and magnetic targeting are conceivable. 15:15 SPECIFIC ABSORPTION RATE OF MAGNETOSOME NANOPARTICLES DISTRIBUTED IN LIQUID AND SOLID MEDIA Authors : M.L. Fdez-Gubieda1, J. Alonso1, J.M. Barandiarán1, A. Muela2, N.A. Usov3, S.A. Gudoshnikov3, O.N. Serebryakova3 Affiliations : 1Departamento de Electricidad y Electrónica, Universidad del País Vasco 6 5 6 6 6 7

8 sur 9 06/05/2013 09:30 (UPV/EHU), Apartado 644, 48080 Bilbao, Spain 2Departamento Inmunología, Microbiología y Parasitología, Universidad del País Vasco (UPV/EHU), Apartado 644, 48080 Bilbao, Spain 3Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation, Russian Academy of Sciences, (IZMIRAN), 142190, Troitsk, Moscow region, Russia Resume : Bacterial magnetosomes, i.e. perfect magnetic nanoparticles extracted from magnetotactic bacteria [1], are of great importance for various biomedical applications, such as targeting drug delivery and magnetic nanoparticle hyperthermia [2], due to their biocompatibility, narrow shape and size distributions and stability of magnetic properties. In the present report we compare the quasistatic and low frequency hysteresis loops for two assemblies of magnetosomes extracted from magnetotactic bacteria Magnetospirillum gryphiswaldense, strain MSR-1, and distributed in liquid and solid media. A sufficiently large specific absorption rate, W = 280 W/g, is obtained for magnetosome assembly in alternating external magnetic field of frequency f = 80 khz and amplitude H = 375 Oe. The numerical simulations of quasistatic [3] and low frequency hysteresis loops are carried for assemblies of isolated nanoparticles, as well as for small clusters of magnetosomes. It is shown that strong magnetostatic interactions between magnetosomes reduce considerably specific absorption rate of an assembly. References 1. R. Herdt, R. Hiergeist, M. Zeisberger, D. Schüller, U. Heyen, I. Hilger, and W.A. Kaiser, J. Magn. Magn. Mater. 293, 80 (2005). 2. Q.A. Pankhurst, N.K.T. Thanh, S.K. Jones, and J. Dobson, J. Phys. D: Appl. Phys. 42, 224001 (2009). 3. N.A. Usov, M.L. Fdez-Gubieda, and J.M. Barandiarán, J. Appl. Phys. 113, 023907 (2013). 15:30 Enhanced magnetic heating properties of microwave-synthesised iron oxide nanoparticles Authors : C. Blanco-Andujar, P. Southern, D. Ortega, Nguyen T. K. Thanh*, Q. A. Pankhurst Affiliations : Davy Faraday Research Laboratory, The Royal Institution of Great Britain, 21 Albemarle Street, London, UK, W1S 4BS Department of Physics and Astronomy, University College London, Gower Street, London, UK, WC1E 6BT ntk.thanh@ucl.ac.uk Resume : The use of alternative techniques for the treatment of cancer to restrict their action to the affected areas has been a major focus in recent years due to the high occurrence of this disease and the limitations of the existing procedures, such as chemotherapy, radiotherapy or surgery. The use of elevated temperatures as a treatment for cancer has the potential to aim for unhealthy cells while leaving unaffected their normal counterparts, as cancer cells are more sensitive to temperatures above 41.8 C.[1, 2] The use of iron oxides in tumour heating was first proposed by Gilchrist et al.[3] in 1957 and, from that moment, more than 4000 reports have been published. Iron oxide nanoparticles have already been used for magnetic hyperthermia leading to promising results as an alternative cancer treatment.[4] Nevertheless, most of these materials are obtained in organic solvents and require complex post-synthesis purification and phase-transfer steps. To this aim, we present the use of a microwave reactor for the simple and easy synthesis of iron oxide nanoparticles by co-precipitation for their use as heating vectors in magnetic hyperthermia. The intrinsic loss power (ILP) generated by the obtained nanoparticle suspensions was studied with a patented Magnetic Alternating Current Hyperthermia (MACH) system working at a frequency of 1MHz and a field amplitude of 10 ka.m-1. A complete physical and morphological characterisation of these materials was also conducted to study their effect on the heating properties. The as-synthesised iron oxide nanoparticles were found to have superior performance in magnetic hyperthermia than the commercial Resovist(R). 1. Jordan, A., et al., Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetic fields in vitro. International Journal of Hyperthermia, 1996. 12(6): p. 705-722. 2. Nielsen, O.S., M. Horsman, and J. Overgaard, A future for hyperthermia in cancer treatment? European Journal of Cancer (Oxford, England : 1990), 2001. 37(13): p. 1587-1589. 3. Gilchrist, R.K., et al., Selective inductive heating of lymph nodes. Annals of Surgery, 1957. 146(4): p. 596-606. 4. Guardia, P., et al., Water-Soluble Iron Oxide Nanocubes with High Values of Specific Absorption Rate for Cancer Cell Hyperthermia Treatment. Acs Nano, 2012. 6(4): p. 3080 3091. 15:45 New magnetic nanoparticles for mahnetic fluid hyperthermia and magnetic resonance imaging Authors : 1 Emil Pollert, 2 Vit Herynek, 3 Pavla Jendelova, 4 Etienne Duguet Affiliations : 1 Institute of Physics, ASCR, v.v.i. Prague,Czech Republic 2 Institute for Clinical and Experimental Medicine, Prague, Czech Republic 3 Institute of Experimental Medicine, ASCR, v.v.i., Prague Czech republic 4 ICMCB, CNRS-UPR 9048, 87, Avenue du Docteur Albert Schweitzer, 33600 Pessac, France Resume : The research and utilization of the magnetic nanoparticles in, e.g., biology and medicine have been preferentially oriented on magnetite Fe3O4 and 6 8 6 9

9 sur 9 06/05/2013 09:30 maghemite g-fe2o3. The complex oxides allow a better control of the magnetic properties in a desirable way. We demonstrate this approach on an example of the La1-xSrxMnO3 perovskites from the point of view of their use in self-controlled magnetic fluid hyperthermia and increase of contrast in magnetic resonance imaging. With materials possessing suitable values of transition temperature TC, coercivity and magnetization, the heating power generated by the nanoparticles was estimated by two independent methods and they were finally employed in vitro and in vivo hyperthermia experiments. Back European Materials Research Society 23 Rue du Loess - BP 20-67037 Strasbourg Cedex 02 - France - Phone:+33-(0)3 88 10 63 72 - Fax:+33-(0)3 88 10 62 93 - emrs@emrsstrasbourg.com

1 sur 9 06/05/2013 09:30 PROGRAM VIEW : 2013 Spring MY PROGRAM : 2013 Spring Symposium : U Design of multifunctional nano-objects for biomedical applications 27 May 2013 28 May 2013 29 May 2013 30 May 2013 31 May 2013 hide a start at Subject Num. Nanoparticles for targeting : C. Menager - C. Billotey 08:30 Amphotericin B conjugated to magnetic nanoparticles stabilized with a bilayer lauric acid, for the treatment of Paracoccidoidiodomycosis. Authors : Ricardo Bentes Azevedo Affiliations : University of Brasilia, Institute of Biological Science, Department Genetics and Morphology. Brasilia - DF, Brasil Resume : Paracoccidioidomycosis, PCM, is a systemic mycosis found in Central and South America. Among the most commonly used drugs for the treatment of PCM stand out Itraconazole and Amphotericin B. The latter has broad spectrum antifungal and potent fungicidal activity. Nevertheless, induces several side effects in humans, particularly nephrotoxicity. In this context, new strategies such as the binding of amphotericin B to biocompatible structures have been developed to reduce its concentration in blood plasma and increasing its delivery to the target organs, and thereby reducing its effects. Among these structures stand out nanostructured materials as magnetic nanoparticles. However, for use in biomedicine these nanoparticles should be biodegradable and non-toxic to the body. In order to develop a system controlled delivery of drugs and reduce side effects of Amphotericin B, this drug was conjugated to magnetic nanoparticles stabilized with bilayer lauric acid. This study aimed to evaluate the efficacy of amphotericin B when coupled to magnetic nanoparticles stabilized bilayer lauric acid, FM-BlaAmB in experimental treatment of PCM. Initially, it was necessary to assess whether this Complex maintain anphotercicin antifungal activity and was toxic or not to mammalian cells. For this, Paracoccidioides brasiliensis, virulent isolate 18 (Pb18), and human mesangial cells and murine peritoneal macrophages were treated in vitro with FM-BlaAmB. The results show that the amphotericin B in the complex FM-BlaAmB sustain an antifungal activity similar to Ambisome? and is not toxic to mammalian cells. Given these encouraging data in vivo tests were conduct. BALB / c mice were infected with the fungus Pb18 and treated with the compound during the acute and chronic forms of the disease for 30 and 60 days. The determination of the fungal load in the lung histopathology of organs such as lung, spleen, liver and kidney associated with quantification of cytokines and the fragmented DNA in bone marrow cells were performed 24 hours after the last treatment. The results show that the amphotericin B in the complex is effective against paracoccidioidomycosis infection in experimental acute, but not chronic infection, and does not induce clinical, biochemical or histopathological changes in liver, kidney or spleen of BALB mice. Moreover, it does not induce genotoxic effects in bone marrow cells of these animals. Therefore, it is reasonable to believe that the Amphotericin B when coupled to magnetic nanoparticles stabilized bilayer lauric acid present similar antifungal capacity against acute infection and does not induce adverse effects at the given doses, and also allows reducing the number of applications in the treatment of PCM in murine. But further studies are needed to improve effectiveness in the treatment of chronic infection. Keywords: magnetic nanoparticles, Amphotericin B, paracoccidioidomycosis 09:00 Feasibility and constraints of particle targeting using antigen-antibody interaction Authors : Viola Tokarova1, Anna Pittermannova1, Vlastimil Kral2, Pavlina Rezacova2, *Frantisek Stepanek1 Affiliations : 1Institute of Chemical Technology Prague, Department of Chemical Engineering, Technická 3, Prague 6, 166 28, Czech Republic, *e-mail: frantisek.stepanek@vscht.cz; 2Department of Recombinant Expression and Structural Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 166 37 Prague, Czech Republic 7 1 7 2

2 sur 9 06/05/2013 09:30 Resume : Target drug delivery systems in the form of nano- or microparticles have attracted attention for their fundamental and practical use. While encapsulation efficiency, stability and release kinetics of active compounds are widely studied, relatively little is known about the adhesion properties of such particles towards real biological substrates under fluid flow conditions. The knowledge of specific interaction of nanoparticles with the target point of release is essential if high specificity is to be achieved and side effects avoided, e.g. in cancer treatment. This work describes the synthesis of mesoporous silica nanoparticles that can act as both diagnostic and therapeutic platform and their surface modification with an antibody fragment (M75). The antibody used in this work specifically binds to tumorassociated antigen (CAIX), which is a membrane protein and gives the possibility to target tumor cells specifically. Adhesion towards pure antigen and towards antigenexpressing cells will be investigated and the surface concentration of the protein will be shown to be a critical success factor for targeting. To simulate physiologically relevant conditions, adhesion studies under fluid flow conditions where a hydrodynamic drag force acts on the particles will be performed in a purpose designed a microfluidic flow-cell. The effect of flow rate, particle size and substrate character on the overall fraction of adhered particles will be investigated. 09:15 Magnetic-Glucose-Nanoparticles: from engineering their in vitro specificity to their in vivo use in tumor targeting. Authors : Valeria Grazú (1), M.aria Moros (1), Berta Saez (1,2), Sara Rivera (1), Isabel Segura (1,2), José Manuel Sanchez Zalabardo (3), Helene Feracci (4), María Luisa García Martín (5), Jesús Martinez de la Fuente (1). Affiliations : (1) Aragon Institute of Nanoscience (INA) University of Saragossa; (2) Aragon Health Sciences Institute (IACS); (3) Hospital Cínico Lozano Blesa ; (4) Centre de Recherche Paul Pascal (CRPP-CNRS); (5) Andalusian Centre for Nanomedicine and Biotechnology (BIONAND) Resume : Mortality due to cancer continues to rise affecting the lives of millions of people worldwide, and therefore early cancer detection is still an area of on-going research. In this sense, magnetic resonance imaging (MRI) has attracted a great deal of interest because of its good image resolution and non-invasive, unlimited tissue-penetration and non-ionizing nature. However, it suffers from inherently low sensitivity, requiring the use of contrast agents such as magnetic nanoparticles (MNPs). In this work we use glucose-mnps (Glu-MNPs) to achieve in vivo tumor vectorization, exploiting the altered metabolism of tumor cells. After founding that an accurate control over the ligand grafting density is needed in order to achieve specific in vitro cell NPs interactions, their in vivo vectorizing capacity was assessed using a human kidney xenograft model. MNPs functionalized with polyethylene glycol were not uptaked by macrophages in vitro but were uptaked in vivo by the liver. This showed that in vivo models are crucial to know the real behaviour of the MNPs. In the case of Glu-MNPs, their uptake by the liver was not surprising as it is an important site of glucose uptake. However, despite this, a high ratio of MNPs were found homogeneously distributed within the tumor. While its is true that further experiments will be required, to study their long-term toxicity and mechanism/s involved in their vectorization, these MNPs seem promising as cancer MRI contrast agents. 09:30 Bioaffinity sensor based on nanoarchitectonic films: control of the specific adsorption of proteins through the dual role of an ethylene oxide spacer Authors : Johanna Davila, Delphine Toulemon, Tony Garnier, Aurélie Garnier, Bernard Senger, Jean-Claude Voegel, Philippe J. Mésini, Pierre Schaaf, Fouzia Boulmedais and Loïc Jierry Affiliations : Centre National de la Recherche Scientifique, Institut Charles Sadron, 23 rue du Loess, BP 84047, 67034 Strasbourg Cedex 2, France; International Center for Frontier Research in Chemistry, 8 allée Gaspard Monge, 67000 Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, Unité 1121, 11 rue Humann, 67085 Strasbourg Cedex, France.; Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 Place de l Hôpital, 67000 Strasbourg, France; Ecole de Chimie, Polymères et Matériaux, 25 rue Becquerel, 67087 Strasbourg Cedex 2, France; Institut universitaire de France, 103 boulevard Saint- Michel, 75005 Paris, France Resume : The identification and the quantification of biomarkers or proteins is a real challenge to allow early detection of diseases. The functionalization of the biosensor surface has to be properly designed to prevent non-specific interactions and to specifically detect the biomolecule of interest. A multilayered nano-architecture, based on polyelectrolyte multilayers (PEM) and the sequential immobilization of streptavidin and a biotinylated antibody, was elaborated as a promising platform for label-free sensing of targeted proteins. Thanks to the versatility of PEM films, the platform was built on two types of sensor surface and was evaluated using both optical and viscoelastic based techniques. A library of 7 3 7 4

3 sur 9 06/05/2013 09:30 biotinylated poly(acrylic acid) (PAA) was synthesized by grafting biotin moieties at different grafting ratios (GR). The biotin moieties were linked to the PAA chains through ethylene oxide (EO) spacers of different lengths. The adsorption of PAA-EOn-biotin (GR) layer on a PEM precursor film allows tuning the surface density in biotin and thus the streptavidin adsorption mainly through the grafting ratio. Non-specific adsorption of serum was reduced and even suppressed depending on the length of EO arms. We showed that to obtain an anti-fouling polyelectrolyte, a grafting of EO9 or EO19 chains at 25% in GR is already sufficient. Thus the spacer has a dual role: ensuring the anti-fouling property and allowing accessibility of biotin moieties. Finally, an optimized platform based on the PAA-EO9-biotin (25%)/streptavidin/biotinylated-antibody architecture was built and demonstrated promising performance as interface architecture for bioaffinity sensing of a targeted protein, in our case ovalbumin. 09:45 Multimodal dendronized carbon nanotube/iron oxide nanoparticles hybrids for imaging and hyperthermia Authors : Antonio GAROFALO,a Gabriella POPA,a Giuseppe LAMANNA,b Cécilia Ménard- Moyon, b Florence GAZEAU,c Claire BILLOTEY,d Alberto BIANCO,b Delphine FELDER- FLESCH,a and Sylvie BEGIN-COLINa Affiliations : a Institut de Physique et de Chimie des Matériaux de Strasbourg UMR CNRS-UDS-ECPM 7504, 23, rue du Loess, B.P.43 67034 STRASBOURG b Institut de Biologie moléculaire et Cellulaire (IBMC), UPR9021 15 Rue R. Descartes, 67084 STRASBOURG c Laboratoire Matière et Systèmes Complexes (MSC), UMR7057 CNRS-INST2I, Université Paris-Diderot, 10 rue Alice Domont et Léonie Duquet, 75205 PARIS cedex 13 d LPCML- Hôpital Edouard Herriot, Université de Lyon 15 place d Arsonval, 69439 LYON Resume : The continuous growing of nanotechnology has brought to many innovations in medicine, particularly revolutionizing the field of imaging and therapy. The main input of nanotechnology in the biomedical field, at the present time, is that it allows a real progress towards temporal and spatial site-specific drug delivery, local therapy, and imaging. In this context, the association of the magnetic properties of iron oxide nanoparticles (NPs) to the characteristics of carbon nanotubes (CNTs) can open new possibilities in the development of multimodal imaging and therapy platforms. A targeted delivery will enhance the efficacy of a treatment by localizing the complex at the site of disease, and it will permit activation and spatial manipulation in vivo via magnetic stimulation. CNTs are promising for biomedical applications as they are capable of crossing many biological and biophysical barriers. Because of their high surface area, CNTs are efficient template for the assembly of nanoparticles and versatile carrier for a wide variety of bioactive molecules. Due to their magnetic properties and mainly their very high transverse relaxivity, functionalized iron oxide NPs are widely developed as negative contrast agent for magnetic resonance imaging (MRI), for therapy with magnetically-induced hyperthermia, and for cell labeling. The development of multimodal contrast agents by functionalization or combination of NPs with other nanomaterials, such as CNTs, could allow reaching effective MRI contrast enhancement, while combining multiple functionalities for therapy. Indeed, NP/CNT hybrids possessing novel magnetic, optical, and thermal properties could offer the potential for imaging, targeting, as well as hyperthermia. Multi-walled CNTs are decorated with iron oxide superparamagnetic NPs. Two different approaches are investigated based on ligand exchange or "click chemistry". We evaluate the potential of the NP/CNT hybrids as contrast agent for magnetic resonance imaging (MRI) and their interactions with cells. The capacity of the hybrids to magnetically monitor and manipulate cells is also investigated. The NP/CNTs can be manipulated by remote magnetic field with enhanced contrast in MRI and they are internalized into tumor cells without showing cytotoxicity. The labeled cells can be magnetically manipulated as they display magnetic mobility and are detected at a single cell level through high resolution MRI. 7 5 10:00 Coffee break Theranostic approach : F. Stellacci - E. Duguet 10:30 Development of novel theranostic platforms: from SPIONs to titanate nanotubes, advantages and comparison with other nanostructures Authors : N. Millot, A.-L. Papa, J. Boudon, R. A. Decréau Affiliations : ICB, UMR 6303 Université de Bourgogne/CNRS, Dijon, France; ICB, UMR 6303 Université de Bourgogne/CNRS, Dijon, France; ICB, UMR 6303 Université de Bourgogne/CNRS, Dijon, France; ICMUB, UMR 6302 Université de Bourgogne/CNRS, Dijon, 8 1

4 sur 9 06/05/2013 09:30 France Resume : Nowadays, nanotechnology offers a large area of applications in medicine and biology, in particular regarding theranostic applications. Two promising nanostructures will be presented in this study and compared with other nanostructures: SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) and Titanate Nanotubes (TiONts). SPIONs represent some of the most important nanoparticles used as MRI contrast agents and for hyperthermia treatment. Here, we present the development of multimodal contrast agents based on functionalized SPIONs for MRI, SPECT (or PET) and Optical Imaging. At first SPIONs are modified by the grafting of organic functions (NH2, COOH or SH) to allow the implementation of more specific organic molecules and among them: macrocyclic chelating agents for nuclear imaging (DOTA) or phthalocyanines derivatives for fluorescence detection and photodynamic therapy. Since the pioneering work of Kasuga et al., a lot of studies have been conducted in the field of titanate nanotubes. Herein, we report the first study on these TiONt-based compounds as potential carriers of therapeutic molecules. TiONts are internalized by various cells via endocytosis and diffusion internalization processes and without inducing cytotoxicity. We are developing these tubes for both in vitro applications (improvement of cardiomyocyte transfection efficiency) and for in vivo developments (improvement of cancer radiosensitivity). Moreover, a systematic study is being carried out to evaluate the biodistribution of TiONt-conjugates in a mouse model. Our results indicate that further development of TiONts might provide a new useful tool for research and clinical therapy in the field of cardiovascular diseases and oncology. 11:00 Magneto-Plasmonic nanoalloys: a new class of multimodal theranostic tools Authors : V. Amendola,1 S. Scaramuzza,1 M. Meneghetti,1 P. Marzola,2 G. Fracasso,3 M. Pinto,3 M. Colombatti3 Affiliations : 1 Department of Chemical Sciences, University of Padova, Padova (Italy) 2 Department of Neurological, Neuropsychological, Morphological and Movement, University of Verona, Verona (Italy) 3 Department of Pathology and Diagnostics, University of Verona, Verona (Italy) Resume : The integration of multiple functionalities in a single object with nanometric size is crucial for the development of efficient tools for nanomedicine applications. Here we show how a synthetic approach based on laser ablation of a solid target in a liquid solution gives access to a library of multifunctional nanomaterials.[1,2,3,4] In particular, we discuss the example of a binary metal alloy in which one of the two elements is a noble metal with plasmonic properties (gold), and the other element is a transition metal with magnetic properties (iron).[5] The structure and surface conjugation of the magneto-plasmonic nanoalloy was engineered in order to gain the functions of a multimodal contrast agent for magnetic resonance imaging, x-ray computed thomography, photoacustic imaging and surface enhanced Raman imaging.[6] The nanoalloy also shows promising performances as near infrared photothermal agent, thus it can be considered as a multimodal theranostic tool. [1] V. Amendola et al; Phys. Chem. Chem. Phys. 11 (20), 3805-3821 [2] V. Amendola et al; Phys. Chem. Chem. Phys., 2013, DOI: 10.1039/C2CP42895D [3] V. Amendola et al; J. Mater. Chem. 21 (11), 3803-3813. [4] V. Amendola et al; Adv. Funct. Mater., 22: 353 360. [5] V. Amendola et al; Coexistence of plasmonic and magnetic properties in Au89Fe11 nanoalloys ; submitted. [6] V. Amendola et al; Multimodal imaging agents based on engineered magneto-plasmonic nanoalloys ; submitted. 11:15 In vitro and in vivo nanotoxicology and biocompatibility testing of coated iron oxide nanoparticles in the selection and development of a multifaceted cancer imaging tool and theranostic drug delivery platform. Authors : Kieran Crosbie-Staunton 1, Adriele Prina-Mello 1,2, Oliviero L. Gobbo 3, Gorka Salas 4,5, Maria del Puerto Morales 4, Yuri Volkov 1,2. Affiliations : 1. Department of Clinical Medicine, Trinity Centre for Health Science, St. James s Hospital, Dublin 8, Ireland; 2. Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin, College Green, Dublin 2, Ireland; 3. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, College Green, Dublin 2, Ireland; 4. Instituto de Ciencia de Materiales de Madrid/CSIC, Sor Juana Inés de la Cruz 3, Cantoblanco, 28049 Madrid, Spain; 5. IMDEA Nanociencia, Faraday 9, Cantoblanco, 28049 Madrid, Spain. Resume : Magnetic iron oxide nanoparticles (MNP) have received considerable attention owing to their potential use as magnetic resonance imaging (MRI) contrast agents, and their ability to be functionalized with cancer targeting moieties. The work presented focuses on the development and validation of in vitro high content screening based toxicity and biocompatibility assays and in vivo biodistribution of MNPs. A range of coated MNPs (aminopropilsilane, dimercaptosuccininc acid, polyacrylic acid, and dextran) with defined core sizes 8 2 8 3

5 sur 9 06/05/2013 09:30 were investigated. Multiparametric high content screening analysis was carried out to evaluate the toxic effect following exposure with coated MNPs in four breast cancer models (MCF7, BT474, MDA231, SKBR3) and a normal-like breast model (MCF10A). Changes in cell count reduction, lysosomal intensity/ph and cell permeability were analysed following 24 h exposure. Post-exposure changes in hydrodynamic diameter of retrieved MNPs were recorded by the Nanoparticle Tracking and Analysis (NTA) technique to gain an understanding of the direct effect of the cell culture environment on MNP stability. In addition, in vivo biodistribution and iron content in organs was evaluated in small animals using a 7T MRI system and the particle electron paramagnetic resonance technique. By adopting a two tier in vitro and in vivo approach, it was possible to identify suitable biocompatible MNPs for further functionalization with cancer targeting moieties 11:30 Dendronized magnetic nano objects for in vivo MR and hyperthermia Authors : A. Walter a, A. Garofalo a, L. Lénaïc c, C. Billotey b, F. Gazeau c, C. Wilhem c, D. Felder-Flesch a, S. Bégin-Colin a Affiliations : a : Institut de Physique et Chimie des Matériaux de Strasbourg, UMR CNRS-UdS 7504, Strasbourg, FRANCE. b: Hospices Civils de Lyon - Service de Médecine Nucléaire Pavillon B, 5 place d Arsonval, 69437 Lyon cedex 03, France c : LMSC, Université Paris Diderot, Laboratoire MSC, Bâtiment Condorcet, 10 rue Alice Domon et Léonie Duquet 75025 Paris - Cedex 13 Resume : Functionalized iron oxide nanoparticles (IONPs) have emerged as one of the most promising nanomaterials for biomedical applications. Indeed IONPs have a large surface area, good magnetic properties and can be designed to provide functional groups for grafting tumor-targeting ligands for diagnostic imaging, delivery of therapeutic agent and hyperthermia. For these applications, designed IONPs are required. Indeed, large and highly magnetic NPs are necessary for magnetic separation, while small NPs are preferred for imaging. For hyperthermia, the amount of heat generated by NPs is highly dependent on NPs structural properties. Most studies have been performed on spherically shaped NPs but the current progress in the IONPs synthesis allows now synthesizing cubic shaped and/or core-shell NPs displaying original properties. Indeed, exchange-coupled magnetic NPs have been recently demonstrated as a new means of modulating magnetism, resulting in a significant enhancement of magnetic heat induction for hyperthermia. We report herein on our work on the synthesis of NPs with different morphologies (spheres, cubes and edges grown cubes) and composition and on their functionalization by dendron molecules which have been proved as efficient bioactive and biocompatible molecules. The structural and magnetic properties of various systems are studied and compared through relaxivity measurements, hyperthermia and in vivo MRI experiments and cells internalization. 11:45 In vitro and in vivo study of theragnostic magnetic nanocarriers of doxorubicin Authors : Juliette Gautier, Emilie Allard-Vannier, Sandra Même, Ambre Carrouée, Emilie Munnier, Katel Hervé-Aubert, Jean-Claude Beloeil, Igor Chourpa Affiliations : Juliette Gautier, Emilie Allard-Vannier, Ambre Carrouée, Emilie Munnier, Katel Hervé-Aubert, Igor Chourpa, EA 6295 «Nanomédicaments et nanosondes», Université F. Rabelais de Tours, France; Jean-Claude Beloeil, Sandra Même, CNRS UPR 4301, Centre de biophysique moléculaire, Orléans, France Resume : This study deals with novel nanocarriers of doxorubicin (DOX) anticancer drug based on polyethylene glycol-coated superparamagnetic iron oxide nanoparticles (NPs) developed as platforms for theragnostic (therapeutic & diagnostic) treatment of cancers. Optical and magnetic properties as well as other physico-chemical characteristics of the DOX-NPs (colloidal stability in spite of the neutral surface, DH ~80 nm, drug loading of ca. 3% w/w) are compatible with theragnostic applications via systemic administration [1]. The NPs stealthiness was confirmed both in vitro (weak activation of the complement system and poor uptake by phagocytes) and in vivo (t1/2 in blood of 76 ± 6 min, elimination mainly directed to liver and spleen) [2]. In order to evaluate the theragnostic potential of DOX-NPs, we studied several parameters such as the contrast in MRI, the efficiency of magnetic targeting to the tumor, the DOX delivery in vitro and in vivo, and the efficiency against tumor growth. TEM images confirmed the entry of nanoparticles in cancer cells, via caveolae endocytosis. In vitro cytotoxicity of DOX-NPs internalized in MDA-MB435 breast cancer cells was delayed but comparable to that of a DOX solution, and no proper toxicity of nanomaterial was detected. A therapeutical protocol in tumorized mice (2mg/kg DOX, 3 injections, n=4 to 6) with application of an external magnetic field provided encouraging preliminary results since lead to significant limitation of tumor growth. After treatment, organs and blood were taken to evaluate the toxicity of the nanoformulation. To finish, MRI data in mice indicated an improved contrast and distribution kinetics of our NPs compared to commercial product Cliavist. References [1] Gautier et al., Int J 8 4 8 5

6 sur 9 06/05/2013 09:30 Pharm 2012, 423(1):16-25 [2] Allard-Vannier et al., Eur J Pharm Biopharm 2012, 81:498 505 12:00 Lunch Nanoparticles for imaging 1 : N. Millot - Nguyen TK Thanh 13:30 The design of nanoparticles for molecular imaging: a multidisciplinary task Authors : Robert N. Muller, Luce Vander Elst, Sophie Laurent, Carmen Burtea Affiliations : Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 7000 Mons and Center for Microscopy and Molecular Imaging - CMMI, 6041 Gosselies, Belgium Resume : Molecular imaging is a young and growing discipline which aims at the development of new diagnostic technologies using specific reporters for the visualization of molecular processes in vivo, and in particular of those involved in pathological mechanisms. Their early detection may represent a decisive advantage for the choice and the follow-up of the therapeutic strategies. Among the contemporary methods of medical imaging, MRI offers the unique advantage of being non-invasive and to furnish simultaneously - and with a high spatial resolution -anatomical, physiological and molecular information. Nevertheless, the quite low efficiency of MRI contrast agents represents a challenge with respect to the improvement of more efficient reporters and to the development of MR protocols adapted to their detection. A contrast agent for MR molecular imaging (MRMI) is a complex assembly made of a magnetic reporter, the?contrastophore?, linked to a vectorizing moiety specific to the structure to be targeted. The specific molecular vector can be selected among peptides identified by phage display or among the non-peptidic mimetics proposed by the literature. The lecture will present an overview of the current state of the field. 14:00 Label-free detection of biotin-streptavidin binding pair by using the near infra-red light responsible plasmonic nanostructures array with controlled nanogap Authors : Shuhei Uchida, Nobuyuki Zettsu, Kazuya Yamamura Affiliations : Osaka University; Nagoya University; Osaka University Resume : In this work, we focused on a label-free detection of biotin-streptavidin binding pair by using the near infra-red light responsible plasmonic nanostructures array with controlled interparticle distance of several tens of nenometers. The nanoshells array were fabricated by a combination of colloidal self-assembly and subsequent He plasma etching under atmospheric pressure. The diameter, interparticle distance, and shape of nanoshells can be tuned with nanometric accuracy by changing the experimental conditions. The biotin-functionalized PS@Au nanoshell array, having 190 nm diameter (inner 150nm PS core, outer 20 nm Au shell) and 120 nm gap distance, exhibited 240 nm RIU-1 and showed 67 nm red-shift of the maximum LSPR wavelength of 808 nm after exposing to 100nM solution of streptavidin for 3h. To further explore the limit of detection (LOD), we performed quantitative LSPR response upon biotin-streptavidin binding for several different concentrations of streptavidin ranging from 10-17M<[SA]<10-7M, revealing that the LOD was found to be 5~10 femtomolar level. This indicated that the coupling of hybridized plasmonic electromagnetic field in PS@Au nanoshell array induced by the nanogap structure improved sensing performance. 14:15 Gadolinium oxysulfide nanoparticles as multimodal imaging agents for T2-weighted MR, X-ray tomography and photoluminescence Authors : Sèmiyou. A. OSSENI, Sévérine LECHEVALLIER, Robert MAURICOT, Marc VERELST Affiliations : Centre d Elaboration de Matériaux et d Etudes Structurales. Université de Toulouse - UPS, 29 rue Jeanne Marvig, BP 94347, 31055 Toulouse, Cedex 4, France. Resume : We have synthetized gadolinium oxysulfide NanoParticles (NPs) doped with other lanthanides (Eu3+, Er3+, Yb3+) via a hydroxycarbonate precursor precipitation route followed by a sulfuration process under H2S/Ar atmosphere at 750 C in order to propose new multimodal nanoplatforms for Magnetic Resonance (MR), X-ray and photoluminescence imaging. Gd2O2S:Eu3+ NPs absorb strongly near UV ( 300-400 nm) and re-emit a strong red light (624nm). They can be easily internalized by cancer cells, and imaged by epifluorescence microscopy with excitation in the NUV (365 nm). They are not cytotoxic for living cells up to 100 µg/ml. Consequently, they are well adapted for in-vitro imaging on cell cultures. Gd2O2S:Eu3+ NPs show also strong transverse relaxivity and strong X-ray absorption allowing their use as contrast agents for T2-weighted MRI and X-ray tomography. Our study shows that Gd2O2S:Eu3+ NPs are sensibly better than 9 1 9 2 9 3

7 sur 9 06/05/2013 09:30 commercial Ferumoxtran-10 NPs as negative contrast agents for MRI. Upconversion emission of Gd2O2S: Er; Yb (1 ; 8%) NPs under infrared excitation (λex = 980 nm) shows mainly red emission ( 650-680 nm). Consequently, they are more specifically designed for in-vivo deep fluorescence imaging, because both excitation and emission are located inside the transparency window of biological tissue (650-1200nm). Magnetic relaxivity and X-ray absorption behaviors of Gd2O2S: Er; Yb NPs are almost similar to Gd2O2S:Eu3+ NPs allowing also their use as contrast agents for T2-weighted MRI and X-ray tomography. 14:30 Multimodal Metal Oxide Nanoparticles As A Tool For Cellular Imaging: From In Silico To In Vivo Applications Authors : Marie-Hélène Delville,1* Sonia L.C. Pinho, 1, 2, 3 Emeline Ribot, 4 Pierre Voisin, 4 Carlos F.G.C. Geraldes, 3 Luís D. Carlos, 2 João Rocha, 2 Affiliations : 1 CNRS, Universite de Bordeaux, ICMCB, 87 avenue du Dr. A. Schweitzer, Pessac, F-33608, France; 2 Departments of Chemistry and Physics, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal; 3 Department of Life Sciences, Faculty of Science and Technology, and Centre of Neurosciences and Cell Biology, University of Coimbra, 3001-401 Coimbra, Portugal 4 Centre de Resonance Magnetique des Systemes Biologiques, UMR 5536 CNRS-Victor Segalen Universite of Bordeaux, Bordeaux, France Resume : Nanoparticles and their control are of great interest from both academic and industrial points of view, with numerous applications in domains such as medicine, catalysis and material sciences. This talk will stress on metal oxide nanoparticles (NPs) and their use as multifunctionnal contrast agents (CAs). Multifunctionnal CAs can provide a multiple targeting and vizualisation of organs or cells with both detectable changes in the MR signal intensity of the target tissue (by changing its MR relaxation properties) and of classical detectable optical signals for example. Magnetic Resonance Imaging (MRI) is indeed one of the most powerful non-invasive diagnostic tools used in medicine. Paramagnetic gadolinium (III) complexes used for in vivo MRI measurements has a full body distribution, decreasing their concentration within the vicinity of a targeted site requiring very high amounts of CA. To overcome this issue, we have proceeded to their chemical grafting on metal oxide NPs (Silica NPs) as an alternative route to change their bio-distribution, with the desired half-lives, inducing their internalization by macrophages, and having a hyper-signal with T1 weighted sequence. We focused on the development of biocompatible NPs with both such high-spin Gd3+ CAs (seven unpaired electrons), and long lasting Eu3+fluorescent probes for targeted imaging to get rid of self-fluorescence. 14:45 Multimodal I-III-VI2 quantum dots for in vivo near infrared fluorescence and magnetic resonance imaging Authors : Gary Sitbon (1), Elsa Cassette (1), Amaury Patissier (1), Benoit Dubertret (1), Marion Helle (2), Lina Bezdetnaya (2), Frédéric Marchal (2), Marine Beaumont (3), Nicolas Lequeux (1), Thomas Pons (1) Affiliations : (1) LPEM, CNRS UMR8213, ESPCI, 10 rue Vauquelin 75005 Paris, France (2)Centre de Recherche en Automatique de Nancy, Nancy-University, CNRS, Centre Alexis Vautrin, avenue de Bourgogne, 54511 Vandoeuvre-lès-Nancy Cedex, France (3) CIC-IT Nancy (Inserm CIT801), CHU de Nancy Brabois, Rue du Morvan, 54511 Vandœuvrelès-Nancy Resume : Fluorescent and magnetic nanoparticles are attractive multimodal contrast agents for both MRI (e.g. for whole body pre-operative detection) and near-infrared (NIR) fluorescence imaging (e.g. for fluorescence guided surgery). Fluorescent semiconductor nanocrystals, or quantum dots (QD), display a size-tunable emission wavelength and high quantum yield (QY), absorption cross section and photostability. They are thus of great interest for NIR imaging. Until recently, QD emitting in the NIR region were composed of toxic elements (e.g. CdTeSe, PbSe), which potential long term release in the body has been a major obstacle for clinical use. We present here the synthesis and characterization of a novel type of bimodal probes based on Cd- and Pb-free CuInX2 (X= S or Se) cores. Their emission wavelength is tunable from 600 to 1100nm. The growth of a ZnS shell on cores increases QY up to 60% in organic solvents. Doping these QD with paramagnetic Mn2+ ions gives them a superparamagnetic behavior, as confirmed by SQUID magnetic measurements. Doping level is characterized under varying synthesis conditions using elemental analysis and electron paramagnetic resonance. Core-shell QD are soluble in water after ligand exchange and optical properties remain stable over long periods of time in vivo. In addition, we confirm the potential use of these probes as MRI contrast agent by measuring longitudinal relaxation rate up to 0,5 s-1.m-1. 9 4 9 5

8 sur 9 06/05/2013 09:30 15:00 Polymer-grafted USPIOs as Thermosensitive Constrast Agents for MRI Authors : A. Hannecart1, D. Stanicki1, L. Vander Elst1, R. N. Muller1, S. Lecommandoux2, J. Thévenot2, C. Bonduel2, A. Trotier3, P. Massot3, S. Miraux3, O. Sandre2, and S. Laurent1 Affiliations : 1: Chimie Générale, Organique et Biomédicale, UMONS, Belgique 2: LCPO UMR5629 CNRS / Université de Bordeaux, France 3: RMSB UMR5536 CNRS / Université de Bordeaux, France Resume : Two commercial statistical copolymers of ethylene oxide and propylene oxide, Jeffamine M-2005 (PEO5-st-PPO36) and M-2070 (PEO46-st-PPO13), exhibiting thermosensitivity (LCST), were grafted onto the surface of ultra-small superparamagnetic iron oxide nanoparticles (USPIOs) using a silanization reaction and an amide-bond coupling. The LCSTs of the polymers in solution were measured by two ways, respectively light scattering and NMR: for M-2005 it is around 15 C by DLS and 25 C by NMR, for M-2070 50 C by DLS and 80 C by NMR, in accordance with the compositions of EO vs. PO. The resulting polymer-grafted USPIOs exhibit a temperature-responsive colloidal behavior, their surface reversibly changing from hydrophilic below LCST to hydrophobic above it. This phenomenon was utilized to design thermosensitive contrast agents for MRI. Transverse relaxivities (r2) of the core-shell nanoparticles USPIO@PEO5-st-PPO36 were measured at frequencies 8.5, 20 and 60 MHz and longitudinal relaxivity (r1) profiles (NMRD) were acquired between 0.01 and 60 MHz at temperatures ranging from 15 to 50 C: at all frequencies, both r1 and r2 relaxivities show a decrease vs. temperature with an inflection point at the LCST (25 C). To illustrate the interest of such polymer-coated USPIOs for temperature mapping by MRI, we show images of sample tubes taken on a low field MR imager (8.5 MHz) with mixed T1/T2-weighted sequences that show a perfect linearity of the signal with temperature between 15 C and 50 C. 15:15 Mn-impregnated mesoporous silica nanoparticles for cell labeling and tracking in MRI Authors : Marc-A.Fortin1, Rémy G.-Nicholas2, Myriam Marc-A.Fortin1, Rémy G.-Nicholas2, Myriam Laprise-Pelletier1, Jean Lagueux1, Pascale Chevallier1, Yves Gossuin3, Sophie Laurent4, Luce Vander Elst4, Freddy Kleitz2 Affiliations : 1-Centre de recherche du Centre hospitalier universitaire de Québec (CR-CHUQ) and Department of Engineering Materials Université Laval (Quebec City), 2-Department of Chemistry Université Laval (Quebec City), 3-Service de physique expérimentale et biologique, Université de Mons 4-Service de chimie générale, organique et biomédicale, Université de Mons Resume : Mesoporous silica nanoparticles (MSNs) represent a significant advance in drug delivery and cell tracking applications. As Mn2+ is already used as a positive cell contrast agent (in the form of MnCl2), the introduction of Mn in the porous network of MSNs would allow to not only label cells and track them with MRI, but also to progressively deliver small amounts of Mn2+ when submitted to acidic conditions. This could be particularly useful for revealing endosomal or tumoric microenvironnements (typical ph of 5). In the present study, manganese oxide was introduced in the porous network of 3-D porosity MSNs. The particles had a narrow size distribution (140 nm diam.) and high porosity ( 60% vol), which was further validated after treatment with Mn. Mn-MSNs were characterised by XPS and FTIR, and the relaxometric properties, measured in various magnetic field strengths (with NMR and NMRD). At 1.41 T, r1 = 8.4 s-1mmol-1 was measured, as well as a r2/r1 = 2. Therefore, Mn-MSNs had very high longitudinal relaxivities for Mn-based contrast agents, with the lowest r2/r1 reported for a Mn-MSN system. An extensive in vitro cell labeling study was performed, followed by MRI visualisation study, confirming the possibility to track cells with Mn-MSNs. Colloidal and chemical stability studies at various ph confirmed that Mn-MSNs could be used to indicate, with MRI, the limited but progressive leaching of Mn2+ ions resulting from acidic ph conditions. 15:30 Multifunctional rare-earth vanadate nanoparticles: luminescent probes, hydrogen peroxide sensors and MRI contrast agents Authors : Mouna Abdesselem(1), Markus Schöffel(1), Isabelle Maurin(2), Olivier Clément(3), Pierre-Louis Tharaux(3), Jean-Pierre Boilot(2), Thierry Gacoin(2), Cédric Bouzigues(1), and Antigoni Alexandrou(1) Affiliations : (1) Laboratoire d Optique et Biosciences, Ecole Polytechnique, INSERM U696 - CNRS UMR7645, Route de Saclay, 91128 Palaiseau, France (2) Laboratoire de Physique de la Matière Condensée, Ecole Polytechnique, CNRS UMR 7643, Route de Saclay, 91128 Palaiseau, France (3) Paris Centre de Recherche Cardiovasculaire (PARCC), INSERM U970 56 rue Leblanc, 75015 Paris, France Resume : Multifunctional particles are of great interest for multimodal imaging in diagnosis and biomedical applications. We synthesized Y0.6Eu0.4VO4 nanoprobes that show red photo-stable, non-blinking luminescence1 with an oxidant-dependant reversible photoreduction. These particles are hence ideal for single-biomolecule 9 6 9 7 9 8

9 sur 9 06/05/2013 09:30 labeling, tracking2, and oxidant sensing. We thus investigated intracellular signaling pathways with both temporal and spatial resolution3. We then developed paramagnetic Gd0.6Eu0.4VO4 particles and proved they are efficient T1-contrast enhancers (r1= 8.2 mm-1s-1at 20 MHz, compared to Dotarem : r1=3.6 mm-1s-1). We moreover showed that these particles retain their luminescent and oxidant sensing properties, and they have the advantage of a low leaching of toxic free Gd3+ from the solid matrix (50 ppm in 15 days at 20 C). We performed T1-weighted MRI monitoring in living mice and revealed a significant contrast enhancement (+35%). We also showed the accumulation of the injected dextrancoated Gd0.6Eu0.4VO4 particles in the bladder 30 minutes after injection. These multifunctional particles are thus very promising for multimodal functional imaging in living animals. 1. E. Beaurepaire, V. Buissette, M.-P. Sauviat, D. Giaume, K. Lahlil, A. Mercuri, D. Casanova, A. Huignard, T. Gacoin, J.-P. Boilot, A. Alexandrou. Nano Lett. 4, 2079-2083 (2004) 2. S. Türkan, J.-B. Masson, A. Alexandrou. Biophys. J., 102, 2288 2298 (2012) 3. D. Casanova, C. Bouzigues, T.-L. Nguyên, R. O. Ramodiharilafy, L. Bouzhir-Sima, T. Gacoin, J.-P. Boilot, P.-L. Tharaux, A. Alexandrou. Nature Nanotechnol.,4(9):581 585 (2009) Back European Materials Research Society 23 Rue du Loess - BP 20-67037 Strasbourg Cedex 02 - France - Phone:+33-(0)3 88 10 63 72 - Fax:+33-(0)3 88 10 62 93 - emrs@emrsstrasbourg.com

1 sur 30 06/05/2013 09:31 PROGRAM VIEW : 2013 Spring MY PROGRAM : 2013 Spring Symposium : U Design of multifunctional nano-objects for biomedical applications 27 May 2013 28 May 2013 29 May 2013 30 May 2013 31 May 2013 hide a start at Subject Num. Nanoparticle design 2 : R. Muller - S. Begin 08:30 Colloidal gold: Functionality, interactions with endothelial cells and beyond. Authors : Dorota Bartczak,(1) Otto L. Muskens, (1) Tilman Sanchez-Elsner, (2) Timothy M. Millar,(2) Antonios G. Kanaras*(1) Affiliations : (1) Institute for Life Sciences, Faculty of Physical and Applied Sciences, University of Southampton, UK, SO171BJ (2) Faculty of Medicine, University of Southampton, UK Resume : Colloidal nanocrystals are employed in several fields of science ranging from biology and medicine and the development of new diagnostic methods, drug delivery, and imaging, to physics and engineering and the fabrication of novel devices for energy conversion and storage. The major reason for the vast range of applications of colloidal nanocrystals is the ability to easily tune the density of their electronic states, which allows the control of their magnetic, optical, electrical, catalytic and mechanical properties, characteristic for different materials. The control over the properties of these nanocrystals can be achieved by chemically adjusting their size, shape, and composition as well as by carefully selecting the organic molecules to coat their surface. In this presentation we will show our recent developments producing strategically engineered nanocrystals and using them in biomedical applications. We will mainly focus on the interactions of colloidal gold nanoparticles and endothelial cells. Endothelial cells are the major players in a vital biological process-the angiogenesis. Angiogenesis is the growth of new capillary vessels to bring oxygen and nutrients at the most distant areas of the body. Manipulation of this process could be the key to the development of several diseases including cancer. We will show our recent efforts towards the manipulation of angiogenesis using bio-functionalized nanoparticles. References [1] D. Bartczak, S. Nitti, T. M. Millar, A. G. Kanaras Nanoscale, 2012, 4 (15), 4470 4472. [2] D. Bartczak, O. L. Muskens, S. Nitti, T. M. Millar, T. Sanchez-Elsner, A. G. Kanaras Small 2012, 8(1), 122-130 [3] D. Bartczak, T. Sanchez-Elsner, F. Louafi, T. M. Millar, A. G. Kanaras, Small 2011, 7, 388 394. [4] D. Bartczak, O. L. Muskens, T. M. Millar, T. Sanchez-Elsner, A. G. Kanaras NanoLett. 2011, 11, 1358 1363 09:00 Fast and simple modification of large gold nanoparticles with DNA Authors : Ron Gill, Kristian Goeken, Tony Gouriye, and Vinod Subramaniam Affiliations : Nanobiophysics Group, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands. Resume : DNA-coated gold nanoparticles are one of the most common multifunctional nanoparticles reported on in literature. The traditional method of modifying gold particles with DNA involves the slow addition of salt to a solution containing the thiolated DNA and gold nanoparticles over several days. While in the last few years several reports of methods for the fast modification of DNA have appeared, most of them are only suited for smaller (<15nm) particles. Here we report on fast and simple modification of large gold nanoparticles using DNA with a positively charged tail. This allows us to shorten the typical incubation times from hours/days to minutes, without any noticeable aggregation during the preparation. We also investigate the role of the thiol at the end of the DNA for both the modification and stability of the particles. 09:15 Facile formation of lipid nanotube networks using external field Authors : Yoshihiro Sasaki, Shinichi Sawada, Kazunari Akiyoshi Affiliations : Graduate School of Engineering, Kyoto University; ERATO, Japan Science and Technology Agency (JST) 10 1 10 2 10 3

2 sur 30 06/05/2013 09:31 Resume : Lipid nanotubes have attracted much attention because of their applications in biotechnology and nanotechnology. Biological lipid nanotubes, known as tunneling nanotubes, that connect biological cells over a long distance were recently discovered as a new cell-to-cell communication system. The work presented here represents a method to facilitate the formation of lipid nanotubes by applying shear flow to surface immobilized liposomes. Fluorescence microscopic images clearly showed tubulation when shear flow was applied to a closed channeled chamber, immobilizing the liposomes via avidin-biotin interactions. In most cases, extended ends of the nanotubes were connected with another liposomes. Strong bias was found in the direction of tubulation, indicating the nanotubes were formed parallel to the direction of fluid flow. The presence of an internal water phase provided by lipid bilayer membranes was also confirmed by using confocal laser scanning microscopy. The nanotubes have a confined space to accommodate at least high molecular weight dextran molecules. The inner spaces of the lipid nanotubes were maintained for at least 5 days. Although the present work represents the initial phase of research in shear stress-induced membrane nanotube formation, the simplicity of this system is promising as an efficient and versatile technique to produce lipid nanotubes for use in biotechnology and nanotechnology. 09:30 Self-Assembly of a Peptide Amphiphile Containing L-Carnosine and its Mixtures with a Multilamellar Vesicle Forming Lipid. Authors : Valeria Castelletto, Ge Cheng, Chris Stain, Che J. Connon, Ian W. Hamley Affiliations : School of Chemistry, Food Science and Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom Resume : The self-assembly of the peptide amphiphile (PA) hexadecyl-(beta alanine-histidine) is examined in aqueous solution,* along with its mixtures with multilamellar vesicles formed by DPPC (dipalmitoyl phosphatidylcholine). This PA, denoted C16-betaAH contains a dipeptide headgroup corresponding to the bioactive molecule L-carnosine. It is found to self-assemble into nanotapes based on stacked layers of molecules. Bilayers are found to coexist with monolayers in which the PA molecules pack with alternating up-down arrangement so that the headgroups decorate both surfaces. The bilayers become dehydrated as PA concentration increases and the number of layers in the stack decreases to produce ultrathin nanotapes comprising 2-3 bilayers. Addition of the PA to DPPC multi-lamellar vesicles leads to a transition to well-defined unilamellar vesicles. The unique ability to modulate the stacking of this PA as a function of concentration, combined with its ability to induce a multi-lamellar to uni-lamellar thinning of DPPC vesicles may be useful in biomaterials applications where the presentation of the peptide function at the surface of self-assembled nanostructures is crucial. *V. Castelletto, G. Cheng, C. Stain, C. J. Connon, I. W. Hamley. Langmuir, 2012, 28, 11599-11608 09:45 New developments on bioconjugated multifunctional nanoparticles for molecular imaging of vulnerable atherosclerosis plaques. Authors : Stéphane Mornet a, Laurent Adumeau a, Julien Boudon a, Etienne Duguet a, Majid Nouhbani b, Marie Josée Jacobin Valat c, Jeanny Laroche-Traineau c, Gisèle Clofent Sanchez c. Affiliations : a ICMCB-CNRS, UPR 9048, Université de Bordeaux 1, 87 av. Dr. Albert Schweitzer, 33608 Pessac, France. b ENSTBB-EA4135 "Biotechnologie des protéines recombinantes à visée santé". c RMSB-CNRS, UMR 5536, Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France. Resume : Atherosclerosis is an inflammatory disease associated with the formation of atheroma plaques liable to rupture. As the risk of plaque rupture is more related to the plaque contents than to the plaque size, a consequence is that the molecular imaging of these plaques has risen as a new imperative. Current studies tend towards the possibility of non-invasive diagnosis, targeting the biological molecules involved in the vulnerable atheroma plaques particularly by Magnetic Resonance Imaging (MRI). Moreover, recent studies point to the importance of platelet?endothelial cell interactions in atherosclerosis-prone arteries at early stages of atherosclerosis and to the prominent role of P-selectin for the initial loose contact between platelets and diseased vessel wall. Herein we describe the used pathway for the designing of multimodal probes based on fluorescent maghemite nanoparticles as MRI contrast agents and fluorescence imaging techniques. This chemical approach will be particularly emphasized by explaining the accurate control of the amount of surface functional groups, directly related to the ability to graft a pre-determined proportion of monoclonal antibodies. Different strategies for the conjugaison with non-immunogenic recombinant antibodies (Ab) and scfv Ab fragments to the functionalized nanoparticles will be presented. The multifunctionality feature of these NPs has allowed, from a set of complementary imaging techniques at multiple scales from cell to animal (ApoE-/- mice), assessing 10 4 10 5

3 sur 30 06/05/2013 09:31 the cellular and molecular targets over-expressed on the vulnerable plaques. 10:00 Coffee break Polymer-based systems 2 : D. Bahadur - E. Duguet 10:30 The effect of PEGylation and dendronization on biodistribution of melanomatargeting ligands studied in vivo by nuclear medical imaging Authors : PARAT Audrey, 1 GAROFALO Antonio, 1 TALEB Jacqueline, 2 BONAZZA Pauline,2 KRYZA David, 2 BILLOTEY Claire,2,3 and FELDER-FLESCH Delphine1* Affiliations : 1 Institut de Physique et Chimie des Matériaux de Strasbourg IPCMS UMR CNRS/UdS 7504 23 rue du Loess BP 43, F-67034 Strasbourg, France. Delphine.Felder@ipcms.u-strasbg.fr 2 Hôpital Edouard Herriot, Bâtiment B, 5 place d Arsonval F-69437 Lyon, France. 3 Service de Médecine Nucléaire Hôpital Nord, Avenue Albert Raimond 42270 Saint-Priest-en-Jarez, Université Jean Monnet - Laboratoire des nanoparticules inhalés LINA & Unité de recherche CTO EA 3738 Resume : The main input of today s Nanotechnology in the biomedical field is to allow real progress in achieving temporal and spatial site-specific drug delivery, local therapy, and imaging. In this respect, creating nano-objects not only displaying very important targeting capacities thanks to a multivalent grafting of biological effectors (multivalent system), but also allowing the vectorization of diagnostic or therapeutic agents through the complexation of very diverse metallic ions is of great interest. The small size of the nanoobjects is mandatory as it allows envisaging a crossing of the capillary barrier, a urinary elimination and a favourable biodistribution. Indeed, our work shows that a dendritic platform combining a high targeting power, favorable biokinetics together with optimal biodistribution properties, drained more predominantly by lymphatic vessels after intradermal injection. We synthetized generation 0 (G0, model compound), 1 (G1) and 2 (G2) PAMAM dendrons bearing 1 (G0), 2 (G1) or 4 (G2) benzamide arylcarboxamide vectors targeting the melanine granules (2). Thanks to a radiolabeling of these dendritic nano-objects with 99mTc or 111In, we showed, that: i) the dendrimer platform improves the biodistribution of the ligand, with a lower unspecific uptake in the liver and a faster elimination of untargeted probes by both urinary and hepato-biliary ways; ii) a 4 ligands/g2 dendrimer platform allows increasing the targeting efficiency. Indeed, it reached 12%/g of tumour at 4h post-iv injection; iii) dendrons G1 and G2 were also radiolabeled with 99mTc, and their lymphatic drainage studied by SPECT after intra-dermic injection at the extremity of lower legs. G2 dendron presented an exclusive lymphatic drainage together with a transient uptake within lymph nodes, starting with the popliteal nodes. The washout of lymph node activity happened within a few hours, and was complete at 24 hours. (1) New Engl. J. Med. 1991, 325, 171; New Engl. J. Med. 1988, 318, 1159. (2) New J. Med. Chem. 2008, 51, 3133. Bioconjugate Chemistry 2009, 20, 760-767; New J. Chem., 2010, 34, 267-275; Biomaterials, 2011, 32, 8562-8573; New J. Chem. invited Perspective review in DENDRIMER 2, 2012, 36 (2), 310-323; Eur. J. Inorg. Chem., invited Microreview on MEMRI Contrast Agents, 2012, 1987-2005. 11:00 Collagen-based fibrillar multilayer films cross-linked by a natural agent Authors : Christophe Chaubaroux1,2, Engin Vrana1,2, Christian Debry1,4, Pierre Schaaf3, Bernard Senger1,2, Jean-Claude Voegel1,2, Youssef Haikel1,2, Christian Ringwald1,2, Joseph Hemmerlé1,2,*, Philippe Lavalle1,2, Fouzia Boulmedais3 Affiliations : 1) Institut National de la Santé et de la Recherche Médicale, INSERM UMR 977, "Biomaterials and Tissue Engineering", 11 rue Humann, 67085 Strasbourg Cedex, France 2) Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'hôpital, 67000 Strasbourg, France 3) Centre National de la Recherche Scientifique, CNRS UPR 22, Institut Charles Sadron, 23 rue du Loess, BP 84047, 67034 Strasbourg Cedex 2, France 4) Hôpitaux Universitaires de Strasbourg, service d Oto-Rhino-Laryngologie, 67098 Strasbourg Cedex, France Resume : Surface functionalization plays an important role in the design of biomedical implants. In this study, we first define a novel nanoscale surface coating composed of collagen/alginate polyelectrolyte multilayers that are cross-linked with genipin for stability. This buildup follows an exponential growth regime versus the number of deposition cycles and exhibits a distinct nanofibrillar structure that is not damaged by the crosslinking step. Stability and cellular biocompatibility of the cross-linked coatings were studied with human umbilical vein endothelial cells. The original surface coating can be covered by a monolayer of vascular endothelial cells within 5 days. Genipin cross-linking renders the surface more suitable for cell attachment and proliferation compared to glutaraldehyde (more conventional 11 1 11 2

4 sur 30 06/05/2013 09:31 cross-linker) cross-linked surfaces, where cell clumps in dispersed areas were observed. As alignment of cells by contact guidance on surfaces has been a key challenge for years, we addressed the topic in the second part of the study. We show the possibility to tune the alignment of three types of cells on mechanically aligned collagen/alginate multilayer films coated on PDMS substrates. In summary, we report a new way to build biocompatible structures with tunable thickness and fibrillar alignment, which would be useful for tissue engineering applications. References: [1] C. Chaubaroux, E. Vrana, C. Debry, P. Schaaf, B. Senger, J.-C. Voegel, Y. Haikel, C. Ringwald, J. Hemmerlé, P. Lavalle, F. Boulmedais, Biomacromolecules 2012, 13, 2128. [2] N. E. Vrana, A. Dupret-Bories, C. Bach, C. Chaubaroux, C. Coraux, D. Vautier, F. Boulmedais, Y. Haikel, C. Debry, M. H. Metz-Boutigue, P. Lavalle, Biotechnol Bioeng 2012, 109, 2134. [3] Z. Y. Tang, Y. Wang, P. Podsiadlo, N. A. Kotov, Advanced Materials 2006, 18, 3203. 11:15 Controlled Synthesis of Positively Charged Polymer Nanoparticles Aimed to sirna Delivery Authors : Dragoni Luca1, Raffaele Ferrari1, Monica Lupi2, Paolo Ubezio2, Davide Moscatelli1, Massimo Morbidelli3 Affiliations : 1Politecnico di Milano, Milan Italy; 2Institute for Pharmacological Research, Milan, Italy; 3ETH Zurich, Zurich, Switzerland; Resume : The ability to silence genes using sirna has a huge potential in the treatment of various genetic diseases. However, the poor stability in biological environment and the biodistribution issues related to sirna make necessary the development of effective carriers. The aim of this work is to synthesize biocompatible and surfactant free positively charged nanoparticles (NPs) with a tunable size suitable for sirna delivery. The NPs have been obtained through a free radical emulsion polymerization, carried out in batch and monomer-starved semi-batch conditions, using a monomer with a cationic charge, hema-choline, as stabilizer and a positively charged initiator. Different particle size have been synthesized using different stabilizer-to-monomer percentage weight ratios, obtaining a simple relationship which can be used to design the final NPs size, down to 15 nm. As a preliminary study for further applications, cell uptake tests on tumor 4T1 cell line, using a functionalized fluorescent sirna have been carried out. This fluorescent sirna has been adsorbed on NPs surface through electrostatic interactions and then cells have been exposed to NPs in order to assess the effectiveness of the NPs as sirna carriers. The results of these tests have shown that NPs are able to bind sirna on their surface and are able to cross cell membranes and thus suitable as sirna vectors for biomedical applications. 11:30 Coupling agent effect on surface complex and magnetic properties of dendronized iron oxide nanoparticles Authors : S. Fleutot(1), A. Walter(1), G. L. Nealon(1), D. Toulemon(1), B.P. Pichon(1), D. Felder-Flesch(1), J-M. Greneche(2), H. Martinez(3), D. Guillon(1), B. Donnio(1), S. Begin- Colin(1) Affiliations : (1) Institut de Physique et Chimie des Matériaux de Strasbourg, UMR CNRS-UdS 7504, Strasbourg, France; (2) Institut de Recherche en Ingénierie Moléculaire et Matériaux Fonctionnels, UMR CNRS 2575, Le Mans, France; (3) Institut Pluridisciplinaire de Recherche pour l Environnement et les Matériaux, UMR CNRS UPPA 5254, Pau, France. Resume : Functionalization of magnetic iron oxide nanoparticles (NPs) by organic molecules is exploited in the intensive research for biomedical applications such as magnetic drug targeting, hyperthermia or MRI, as well as for a bottom-up approach to build nanodevices such as high density storage systems. Even though it is well-established that the magnetic properties of iron oxide NPs are strongly dependent on their synthetic routes, their size and/or their composition, the specific influence of the inorganic-organic bonding (and therefore of the surface state) on the magnetic properties of functionalized NPs is still an open question. In this context, the ligand coordination of the anchoring group onto the surface of magnetite NPs has been investigated using either phosphonate or carboxylate groups as a function of the grafting strategy and solvents. Oleic acid coated 10 nm sized NPs obtained by thermal decomposition have been functionalized by dendron molecules either by direct ligand exchange in organic solvents or by a ligand exchange process including a phase transfer in water leading to very stable water suspensions at ph=7.0. The NPs have been characterized before and after grafting by several techniques (TEM, IR, XRD). Complementary in-field Mössbauer, XPS and SQUID measurements have allowed a better understanding of the effect of the coupling agent and of the grafting process on the nature of the surface complex and on the spin canted layer at the surface of the NPs. 11 3 11 4

5 sur 30 06/05/2013 09:31 11:45 Development of biodegradable nanoparticulate scaffolds for cardiovascular implants Authors : V. Karagkiozaki1, A.M. Pappa1, S. Krol2, P. Kavatzikidou1, P. G. Karagiannidis1, S. Logothetidis1 Affiliations : 1. Νanomedicine Group, Department of Physics, Lab for Thin Films -Nanosystems & Nanometrology, Aristotle University of Thessaloniki, Greece 2. Fondazione IRCCS Neurologic Institute Carlo Besta, IFOM-IEO-campus, Italy Resume : Cardiovascular diseases are the leading cause of death worldwide with more than 1.5 million percutaneous coronary revascularization procedures such as intracoronary stenting, performed annually. A major clinical problem is late stent thrombosis after implantation of drug eluting stents (DES) which is caused mainly by the polymers used as drug reservoirs that delay the stent endothelialization. To address this drawback, we developed electrospun biodegradable poly-εcaprolactone (PCL) scaffolds which were embedded with biodegradable nanoparticles loaded with anti-inflammatory/or -platelet drugs. Size, z-potential, drug loading and release measurements were made for nanoparticle characterization. Cell studies follow to test the safety and effectiveness of the scaffolds to promote endothelial cells adhesion and proliferation. The cytocompatibility of the nanoscaffolds was evaluated by MTT assay in line with imaging studies as compared to controls and drug-free PCL scaffolds. By this process, polymer fibers with diameters from 100-500 nm were fabricated. Alterations in deposition parameters, polymer concentration and solvents were found to determine the structural properties of the scaffolds for favorable cell response. The results revealed that such scaffolds were cytocompatible exhibiting great potential to be applied for cardiovascular engineering applications. Acknowledgments: This work has been partially supported by the NanoCardio Project Nanomedicine for Advanced, Bioactive/-mimetic materials for Cardiovascular Implants, funded by GSRT Greece and European Commission. 11 5 12:00 Lunch Nanoparticle design 3 : A. Kanaras - C. Billotey 13:30 Magnetic hybrid systems for nanomedicine applications Authors : G. Béalle, A. Seth, P. Hugounenq, A. Abou-Hassan, J.-M Siaugue, C. Ménager Affiliations : University Pierre et MArie Curie (UPMC) Resume : The use of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) for nanomedicine applications is based on their physical properties. Each particle can be considered as a magnetic monodomain with a magnetic moment. This magnetic moment disturbs the water proton relaxation and allows the use of USPIO as imaging contrast agent in magnetic resonance imaging (MRI). Under an oscillating magnetic field this magnetic moment can rotate inducing a thermal dissipation, this phenomenon is called magnetic hyperthermia. When the magnetic nanoparticles are embedded in a complex system (liposomes, polymersomes, microgels) it is possible to vectorize the magnetic systems under a magnetic field gradient for in vivo targeting. On overview of the design of magnetic systems for nanomedicine applications will be given from the chemistry of the nanoparticles themselves (nanoflowers, core-shell) to the design of hybrid magnetic systems by different processes (reverse phase evaporation, microfluidic). Magnetic particles densely trapped into liposomes (lipid vesicles) have been used to target tumors in vivo and exhibit very interesting properties as contrast agents but also as nano-heaters for hyperthermia applications. An alternative approach can be to decorate membrane of cells or vesicles with nanoparticles in order to bring new functionalities to the system. 14:00 Temperature nanoprobes based on Hybrid nanocolloids Authors : P. André,1,2 S. Chen,1 C. Hoskins,3 L. Wang,3 M.P. MacDonald3 Affiliations : 1 School of Physics and Astronomy (SUPA), University of St Andrews (St Andrews, UK) 2 RIKEN Advanced Science Institute (Wako, Japan) 3 Institute for Medical Science and Technology, University of Dundee (Dundee, UK) Resume : Multimodal nanoparticles (nps) are a growing component of biomedical research activity with for instance dual imaging demonstration taking advantage of designing nanoparticles with combined optical and magnetics properties. Further interest has recently been attracted for temperature measurement in biological media.[1-2] Stepping aside of imaging we have recently demonstrates that hybrid nanocolloids can be designed and used to create nanoprobes for remotely sensing temperature of aqueous media.[3-4] Such multi-modal nanocolloids combine 12 1 12 2

6 sur 30 06/05/2013 09:31 development opportunities not only for multimodal magnetic-optical imaging but also for non-invasive and remote absolute temperature optical monitoring suitable for hyperthermia treatments and cell poration. The presentation will present our last results and discuss the criteria associated with the design of colloidal temperature nanoprobes suitable for biomedical applications. [1] D. Jaque, F. Vetrone, Nanoscale 2012, 4, 4301. [2] C. D. S. Brites, P. P. Lima, N. J. O. Silva, A. Millan, V. S. Amaral, F. Palacio, L. D. Carlos, Nanoscale 2012, 4, 4799. [3] P. André, M. MacDonald, S. Chen, UK Patent PE954566GB, 2011. [4] S. Chen, C. Hoskins, L. Wang, M. P. MacDonald, P. André, Chem. Comm. 2012, 48, 2501. 14:15 FeBi nanohybrids for biomedical applications Authors : Catherine Amiens,1 Frédéric Pelletier,1 Jean-Gabriel Mattei,2,3 Diana Ciuculescu,1 Marie-Jos? Casanove,2 Pierre Lecante,2 Nader Yaacoub,4 Jean-Marc Gren?che 4, Jean-Charles Dupin,3 Joachim Allouch,3 Danielle Gonbeau3 Affiliations : 1 Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, BP44099, 31077 Toulouse, France; 2 CNRS; CEMES (Centre d'elaboration des Matériaux et d'etudes Structurales); BP 94347, 29 rue J. Marvig, F-31055 Toulouse, France et Université de Toulouse ; UPS ; F-31055 Toulouse, France; 3 Université de Pau et Pays Adour, CNRS, IPREM, ECP,UMR 5254, F-64053 Pau 09, France; 4 LUNAM Université du Maine, Institut des Molécules et Matériaux du Mans IMMM, UMR CNRS 6283, F-72085 Le Mans, France Resume : Bismuth is interesting due to its physical properties (high diamagnetism, high X-Ray absorption coefficient?)1 and because of its relatively low toxicity despite being one of the heaviest elements.2 It is thus an ideal partner to iron in biomedical applications, to be compared with the FeAu system already widely studied,3 but with the added advantage of a much lower cost. Moreover, iron and bismuth present very different structural features such as atomic radii, crystalline structure? inducing their total immiscibility in the bulk state, or in thin films. Consequently, the iron/bismuth system is well adapted to afford heterodimers or core/shell nanohybrides. Using an organometallic approach, we have prepared the first FeBi nanoparticles.4 Their characterization by shows that their chemical order is particularly well adapted to biological applications such as contrast agents for MRI and CT imaging. 1. E. I. Rogacheva, S. G. Lyubchenko, M. S. Dresselhaus, Thin Solid Films, 516 (10), 3411-3415 (2008). 2. R. Mohan, Nature Chemistry, 2, 336 (2010). 3. See for example: Y-N. Wu, L-X. Yang, X.-Y. Shi, I-C. Li, J. M. Biazik, K. R. Ratinac, D-H. Chen, P. Thordarson, D-B. Shieh, F. Braet, Biomaterials, 32(20), 4565 (2011) 4. J. G. Mattei, F. Pelletier, D. Ciuculescu, P. Lecante, J.C. Dupin, N. Yaacoub, J. Allouche, J. M. Greneche, D. Gonbeau, C. Amiens, and M.J. Casanove, J. Phys. Chem. C, http://dx.doi.org/10.1021/jp309408j 14:30 Magnetic and Fluorescent Hybrid Silica Nanoparticles Based on the Co-encapsulation of gamma-fe2o3 Nanoparticles and [Mo6Br14]2- Luminescent Nanosized Clusters by Water-in-oil Microemulsion; Toward Magnetic, Fluorescent and Plasmonic Nanostructures Authors : Nicolas Nerambourg, Tangi Aubert, Chrystelle Neaime, Fabien Grasset, Stéphane Cordier, Michel Mortier and Gilles Patriarche. Affiliations : Nicolas Nerambourg; Tangi Aubert; Chrystelle Neaime, Fabien Grasset; Stéphane Cordier; Chimie du Solide et Matériaux, UMR 6226 CNRS, Institut des Sciences Chimiques de Rennes, Université de Rennes1, Campus de Beaulieu, CS 74205, 35042, Rennes, France. Michel Mortier; UMR 7574 CNRS, Laboratoire de Chimie de la Matière Condensée de Paris (ParisTech), Ecole Nationale Supérieure de Chimie Paris, F-75005 Paris, France Gilles Patriarche; CNRS, UPR 20, Lab Photon & Nanostruct, F-91460 Marcoussis, France Resume : The design, synthesis and characterization of magnetic-luminescent nanoparticles (MLPs) is now more and more studied since the last decade. Indeed, the association of two distinct entities which possess independently magnetic and luminescent properties within a single nanoparticle (NP) is a great of interest in the field of nano- and biotechnology and nanomedicine. Such bimodal hybrid nanoparticles are particularly suitable for in vitro and in vivo bioimaging applications such as MRI and fluorescence microscopy, cell tracking, magnetic separation and visualization, as well as diagnostic and therapeutic agent, so called Theranostic applications. This contribution highlights our efforts to elaborate and to characterize magnetic and luminescent silica nanoparticles, based on the co-encapsulation of luminescent [Mo6Br14]2- nanosized cluster units and γ-fe2o3 nanoparticles (MNPs) of different sizes. Indeed, [Mo6Br14] cluster units exhibits red/infrared stable luminescence emission, which is of great importance for biological applications. The encapsulation of both cluster units and MNPs has been achieved through the water-in-oil (w/o) microemulsion process, which is a very well suited method to obtain monodispersed multifunctional NPs with a diameter below than 50 nm. These core-shell systems possess luminescent and magnetic properties, which are both depending of the magnetic core size. Based on the same 12 3 12 4

7 sur 30 06/05/2013 09:31 concept, we succeed to elaborate plasmonic, magnetic and luminescent NPs. 14:45 FLUORESCENT SILICA NANOPARTICLES BASED ON ORGANIC AND INORGANIC FLUOROPHORES: PREPARATION AND CHARACTERIZATION Authors : C.S. Neves (1), C. M. Granadeiro (1), S. S. Balula (1), L. Cunha-Silva (1), D. Ananias (2), S. Gago (3), G. Feio (4), P. A. Carvalho (5), E. Pereira (1), P. Eaton (1) Affiliations : (1) REQUIMTE, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, 4169-007 Porto, Portugal; (2) CICECO, Departamento de Quimica, Universidade de Aveiro, 3810-193 Aveiro, Portugal; (3) REQUIMTE, Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Monte de Caparica, Portugal; (4) CENIMAT/I3N, Departamento de Ciencia de Materiais, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; (5) ICEMS, Departamento Bioengenharia, Instituto Superior Tecnico, Universidade Tecnica de Lisboa, Av. Rovisco Pais 1049-100 Lisboa, Portugal Resume : Imaging agents such as fluorescent silica nanoparticles (NPs) that can incorporate organic or inorganic fluorophores have overcome many limitations of conventional contrast agents. In this work we have prepared fluorescent core/shell NPs using organic (rhodamine B isothiocyanate - RBITC) and inorganic (lanthanide-based polyoxometalates - LnPOMs) molecules as the source of fluorescence. Fluorescent silica NPs were synthesized by hydrolysis and polymerization of tetraethylorthoslicate with aqueous ammonia in a water-in-oil microemulsion.[1-2] In the case of silica NPs containing rhodamine B molecules, the dye was firstly coupled to a silane coupling agent and the reaction product was incorporated into silica spheres using the reverse microemulsion technique. The NPs were then characterized by fluorescence spectroscopy, TEM and DLS. We have produced fluorescent silica NPs with a mean diameter of around 70 nm. Fluorescent NPs having LnPOMs as fluorophore were also prepared. The LnPOMs used were the Keggin derivatives [PW11O39Eu(H2O)3]4- and [Eu(PW11O39)2]11-. The NPs were characterized by FT-IR, FT-Raman, 31P MAS NMR, TEM-EDS and ICP analysis where the stability of the material and the integrity of the incorporated europium compound were examined. The nanocomposites exhibit a core/shell structure with mean diameters of approximately 16 nm and 51 nm. Moreover, the silica surface of the NPs was functionalized to enable biomolecule binding. 15:00 Patterned neuronal networks using nanodiamonds and the effect of varying nanodiamond properties on neuronal adhesion and outgrowth Authors : Robert Edgington a, Agnes Thalhammer b, Joseph Welch a, Alexandre Bongrain c, Philippe Bergonzo c, Emmanuel Scorsone c, Richard B. Jackman a, Ralf Schoepfer b Affiliations : a London Centre for Nanotechnology and Department of Electronic and Electrical Engineering, University College London, 17-19 Gordon Street, London, WC1H 0AH, UK b Laboratory for Molecular Pharmacology, NPP, University College London, Gower Street, London, WC1E 6BT, UK c CEA, LIST, Diamond Sensors Laboratory, F-91191 Gif-sur-Yette, France Resume : Detonation nanodiamond monolayer coatings are exceptionally biocompatible substrates for in-vitro cell culture. However, the ability of nanodiamond coatings of different origin, size, surface chemistry and morphology to promote neuronal adhesion has yet to be investigated. Herein, the ability of various nanodiamond coatings of different type to promote neuronal adhesion is investigated and the resulting universal promotion of neuronal adhesion on all nanodiamond coatings is discussed with respect to coating parameters to infer the mechanisms behind neuronal attachment and subsequent outgrowth. Various nanodiamond coatings of different origin, size, aggregation and deposition method have been investigated for their ability to support neuronal adhesion and all ND coatings are shown to universally promote murine hippocampal neuronal adhesion. In particular interest, predominantly oxygenated (untreated) and hydrogenated, fixated nanodiamond coatings show no apparent differences in their ability to promote neuronal adhesion. The possible mechanisms for neurons adhering to ND coatings are discussed, and via parametric correlation coefficient analysis of the morphological properties of ND coatings and their corresponding neuronal cultures, the small radii of curvature of NDs, and thereof their ability to adsorb ECM proteins in their functional state, is implicated as a determining factor in the ability of ND coatings to support neuronal adhesion and growth. Using photolithography and reactive ion etching, nanodiamond patterns are fabricated and the direct patterning of neuronal adhesion using nanodiamond is demonstrated, making ND patterning a promising technique for the in vitro study of ordered neuronal networks without using additional biomolecules to promote adhesion. Furthermore, patterned ND coatings show great potential for directing neurons towards electrodes of neuroprosthetics such as artificial retina microelectrode arrays or cochlear implants. 12 5 12 6

8 sur 30 06/05/2013 09:31 15:15 Optimising the Synthesis of Transferrin grafted Silica Nanoparticles for use as a Targeting Platform Authors : Delyan R. Hristov1, Paolo Verderio2, Eugene Mahon1, Philip Kelly1, Kenneth A. Dawson1 Affiliations : 1 Centre for BioNano Interactions, University College Dublin, Dublin, Ireland 2 University of Milano-Bicocca, Milan, Italy Resume : The development of targeting systems that can discriminate between the tissues in the body so as to deliver drugs specifically or be used for imaging is of upmost importance and has recently been pursued by many research groups[1]. Transferrin as a targeting motif has shown potential as a non-immunogenic targeting vector and thus has potential in anti-cancer treatments since cancer cells typically over express the Tf receptor[2]. An in lab method for synthesising fluorescent silica nanoparticles with grafted Tf was developed and optimized for biological application. The particles were initially synthesised and surface activated by aminopropyltrimethoxysilane (APTMS) condensation by optimised protocols. There is an emphasis on the importance of the initial amine functionalized surface and its importance for the specific uptake of the final protein grafted particle. Bifunctional linker molecules were used to conjugate Transferrin at the particle surface. Following extensive characterisation the biological functionality of the resultant particles was then investigated by testing on cancerous lung cells (A459) where the uptake and specific uptake are observed. To ensure high quality, reproducibility has been carefully considered for the presented syntheses. Results are presented as averages from those results and standard deviations are provided. 1. E. Mahon, A. Salvati, F. Baldelli Bombelli, I. Lynch and K. A. Dawson, Journal of Controlled Release, 2012. 2. M. F. Macedo and M. Sousa, Inflammation & Allergy-Drug Targets, 2008, 7, 41-52. 15:30 Core-Shell Luminescent Nanoparticles for Biomedical Applications. Authors : Nelsi Zaccheroni, Sara Bonacchi, Damiano Genovese, Riccardo Juris, Marco Montalti, Luca Prodi, Enrico Rampazzo Affiliations : Department of Chemistry G. Ciamician, University of Bologna, Italy Resume : Luminescence finds important applications in different fields including medicine. In particular the advent of nanotechnology has introduced the possibility to take advantage of nanostructures as very promising platforms for the design of new luminescent materials with tailored features. We have recently proposed a new versatile synthetic approach that allows to obtain very mono-disperse, water soluble nanoparticles (NPs) with a silica core (10 nm diameter) and an organic shell (7 nm thick) that can host a considerable number of dyes even of different nature. The fluorophores can be irreversibly included during the synthesis and the resulting NPs are brightly luminescent and photostable.(1) Moreover, thanks to efficient intra-particle energy transfer processes, the spectral profile of the emission as well as the excitation wavelength of the NPs can be easily tuned making them suitable for multiplexed analysis. Their chemical versatility also allows an easy modification of the terminal groups of the organic shell to permit the coupling with suitable biomolecules for specific target recognition. Examples of in-vivo, ex-vivo and in-vitro imaging will be presented. (1) S. Bonacchi, S.; Genovese, D.; Juris, R.; Montalti, M.; Prodi, L.; Rampazzo, E.; Zaccheroni, N. Angew. Chem. Int. Ed. 2011, 50,4056-4066. 15:45 New biocompatible nanoparticle click functionalization: photochemical thiol-yne reaction, towards double chemoselective functionalization. Authors : E. Guenin, E. Nehlig, P. Demay Drouard, J. Hardouin, L. Motte Affiliations : Université Paris 13, Sorbonne Paris Cité, France Resume : In a decade click chemistry has emerged as the method of choice for the coupling of a large panel of molecules onto various surfaces. In the domain of nanobiomedecine the use of click chemistry becomes predominant among the plethora of existing functionalization methodologies due to its versatility, easiness, selectivity and of course biocompatibility. Among all the reactions suitable to be named as click reactions, the Huisgen 1,3 cycloaddition between an azide and an alkyne (CuAAC) is from far the most popular one. It has been extensively used in nanoscience. Here we want to report the use of a new biocompatible click functionalization of nanoparticles. Thiol-yne reaction is metal free, water compatible radical reaction that can be done photothermically. Moreover thiol-yne reaction presents another advantage that makes it really suitable for surface chemistry: since the reaction allows two consecutive additions of thiols onto the alkyne, high surface density of the grafting could be reached quite easily. So ongoing with our research on the development of multimodal nanoplateform with aim in biomedical and catalysis applications, we studied thiol-yne functionalization of iron oxide superparamagnetic nanoparticles. We used a nanoplateform consisting of g-fe2o3 nanoparticles coated by a bifunctional molecule from bisphosphonic acid 12 7 12 8 12 9

9 sur 30 06/05/2013 09:31 family presenting alkyne functions on its surface. We evaluated the photochemical coupling of various thiol molecules and biomolecules. We also investigated multiple click chemistry coupling onto this nanoplateform. To our knowledge this work represents the first functionalization of nanoparticles by thiol-yne reaction and the first double click process on the same nanoparticle surface. 15:55 Coffee break Poster session : - 16:00 Enhanced Performance of Biodegradable Poly(butylene succinate)/graphene Oxide Nanocomposites via in situ Polymerization Authors : Xiaowei Wang, Gexia Wang, Junhui Ji Affiliations : Technical Institute of Physics and Chemistry, Chinese Academy of Sciences Resume : Poly(butylene succinate) (PBS)/graphene oxide (GO) nanocomposites were facilely prepared via in situ polymerization. The properties of the nanocomposites were studied using FTIR, XRD, 1HNMR, and the state of dispersion of GO in the PBS matrix was examined by SEM. The crystallization and melting behavior of the PBS matrix in the presence of dispersed GO nanosheets have been studied by DSC and polarized optical microscope. Through the mechnical testing machine and dynamic thermomechanical analysis, PBS/GO nanocomposites with 3 wt% GO have shown a 43% increase in tensile strength and a 45% improvement of storage modulus. These high performances of the nanocomposites are mainly attributed to the high-strength property of graphene oxide combined with the strong interfacial interactions in the uniformly dispersed PBS/GO nanocomposites. 16:00 Novel morphology magnetic FePt clusters and elucidation of the mechanism of formation Authors : Luke A. W. Green (ab), Trinh T. Thuy (c), Derrick Mott (c), Shinya Maenosono (c), Quentin A. Pankhurst (ab), and Nguyen T. K. Thanh (ab) * Affiliations : (a) University College London, Gower street, London, WC1E 6BT, United Kingdom. (b) The Royal Institution of Great Britain, 21 Albemarle street, London, W1S 4BS, United Kingdom. (c) Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan. Resume : We report the controlled synthesis of novel morphology magnetic FePt clusters composed of platinum rich FePt nanocrystals within an iron rich FePt alloy. Cluster size increases with increasing total surfactant amount. Polycrystalline clusters up to 54 nm composed of crystals of 4 nm in diameter are observed. Clusters of 44 nm in diameter exhibit magnetic saturation (MS) of 30 emu.g-1 not previously observed in the literature. With a decrease in the amount of oleic acid, increased size and monodispersity of clusters up to 54 nm is observed, while excess oleic acid promotes monocrystalline NPs in the order of 8 nm. Coordination of Fe and Pt atoms with OA and OLA respectively hinders deposition of each respective metal in NP growth. The use of aromatic bulky dibenzyl ether over aliphatic linear dioctyl ether resulted in clusters with improved monodispersity. Transmission electron microscopy, dynamic light scattering, X-ray diffraction, super-conducting quantum interference device magnetometry, scanning transmission electron microscopy, energy dispersive X-ray spectroscopy, inductively coupled plasma atomic emission spectroscopy, X-ray photoelectron spectroscopy and Fourier transform infra-red spectroscopy analyses are presented and discussed. 16:00 AC magnetic field triggered multiple drug delivery by mesoporous superparamagnetic Fe3O4 nanoparticles Authors : Lina Pradhan, R. Srivastava, D. Bahadur Affiliations : Centre for Research in Nanotechnology & Science; Biosciences and Bioengineering; Department of Metallurgical Engineering and Materials Science Indian Institute of Technology Bombay, Powai, Mumbai 400076, India Resume : Multiple drug encapsulated mesoporous superparamagnetic Fe3O4 nanoparticles (MSNPs) have been investigated for in vitro thermo-chemotherapy. The mesoporous nature of Fe3O4 was observed by TEM. The porous behavior has further been confirmed from porosity measurement. MSNPs exhibit high magnetization value of ~80 emu/g. And it has the ability to generate hyperthermia temperature (~43 C) with 1 mg/ml in 10 min. The entrapment efficiency of multiple drugs such as both Doxorubicin (hydophilic):paclitaxel (hydrophobic) is ~84:44% (~21:11 µg/ml) and Doxorubicin:Cisplatin (hydrophobic) is ~92:45% (~23:11 µg/ml). The ph dependent sustained release behavior of multiple drugs is observed. But dual drug release efficiency is enhanced under external application of 1 2 3

10 sur 30 06/05/2013 09:31 AC magnetic field (ACMF). So, drug release can be better controlled using ACMF for in vitro thermo-chemotherapy. The cytotoxicity efficacy is enhanced with combined drugs compared to individual in different cancer cell lines such as MCF-7, MDA-MB-231 and PC3. Confocal microscopy confirms the cellular uptake of multiple drugs encapsulated with MSNPs. The cell growth inhibition is enhanced with dual drug in the presence of ACMF compared to absence of ACMF. Our approach of multiple drug carrier system is potential of giving synergistic effect of both chemo thermo therapies towards cancer treatment. 16:00 Synthesis of Pt based Bi-metallic Magnetic Nanoparticles using Atmospheric Microplasmas Authors : Ying Wang 1, Rohit Medwal 2, Hai Liu 3, Tan Kin Seng 1, A. Talebitaher 1, P. Lee 1, T. L. Tan 1, R. V. Ramanujan 3, Yizhong Huang 3 and R. S. Rawat 1 Affiliations : 1. NSSE, NIE, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616; 2. Department of Physics and Astrophysics, University of Delhi, Delhi, India 110007; 3. School of Material Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798; Resume : An atmospheric microplasma (AMP) method was explored for Pt based bi-metallic magnetic nanoparticle synthesis. The anodic atmospheric microplasma discharge was conducted between the syringe needle of bore diameter less than 700 µm and the Pt based chemical solution using high voltage DC power supply. The helium, at flow rate of 50 cubic centimeters per minute at STP (SCCM), was used as the discharge medium; and the AMP discharge was conducted for discharge current magnitude, different discharge durations and different molar concentration of the solutions. Under optimized conditions, the Pt based bi-metallic magnetic nanoparticles were synthesized at room temperature AMP discharge within 10 minutes. The bi-metallic magnetic nanoparticles were then characterized for their morphological, structural and magnetic properties using various characterization techniques. 16:00 Silica nanoparticles grafted to hydrophobically alkali-swellabe polymers as topical skin protectant Authors : Arnaud Zenerino (a), Sonia Amigoni (a), Elisabeth Taffin de Givenchy (a), Denis Josse (b), Guittard Frédéric (a) Affiliations : (a) Université de Nice - Sophia Antipolis, Laboratoire de Physique de la Matière Condensée, Equipe Surfaces et Interfaces, parc valrose, 06108 nice cedex 2, France; guittard@unice.fr (b) Institut de recherche biomédicale des armées, département de toxicologie, unité protection-décontamination, 24 avenue des maquis du grésivaudan, 38700 La Tronche et Service Départemental d Incendie et de Secours des Alpes-Maritimes, 140, Avenue de Lattre de Tassigny, BP99, 06271 Villeneuve-Loubet Cedex Resume : In domestic, occupational, professional and incidental contexts, skin can be exposed to toxic chemicals like pesticides for example. As a consequence, the development of suits and topical products to protect the skin against toxic chemical agents is necessary.[1] Topical skin protectant (TSP) constituted of low wettability perfluorinated polymers and inorganic nanoparticles have received a great interest because of their unique physical and chemical properties like their adsorption and/or degradation properties as a function of the nanoparticles used.[2,3] To combine both nanoparticles and perfluorinated copolymers in the same TSP in order to increase its effectiveness, we propose the synthesis of a new nanocomposite containing silica nanoparticles grafted to a rheological modifier such as hydrocarbon or fluorocarbon ASE or HASE polymers, in order to obtain effective barrier properties against toxic chemical agents. ASE (alkali-swellable emulsion) or HASE (hydrophobically alkali-swellable emulsion) polymers have been extensively studied due to their ability to form three-dimensional networked gels. They are currently found in cosmetic products, paints and anti-icing fluids. The backbone of these copolymers is constituted of acrylic acid (AA), monomers with short hydrophobic chain and small amounts of hydrophobic pendant groups (macromonomers). These thickening agents typically combine two properties: the solubility in alkaline solution due to the presence of carboxylic groups that ionise and provoke an increase of hydrodynamic volume, and the existence of Van der Walls interactions between the polymeric chains for an increase of the aqueous solution viscosity.[4] The main difficulty encountered in nanocomposites is the stability of the nanoparticles dispersion in the surrounding substance. This parameter is also of crucial importance to obtain an optimum protection against chemical agents. In our work, dynamic light scattering was used to measure the dispersion of nanoparticles in suspensions constituted of nanoparticles grafted onto thickeners. In addition, coatings of polymers were made on glass slides and the dispersion of nanoparticles was characterized by Atomic Force Microscopy (AFM). The skin protective effectiveness of these products against one organophosphorus model compound (paraoxon) was evaluated by using in vitro tests. Toxicological tests with 4 5

11 sur 30 06/05/2013 09:31 microorganisms were used to show that the polymer/nanoparticles nanocomposite was environmentally safe.[5] Acknowledgments. We acknowledge Délégation Générale de l Armement, Service de Santé des Armées for their grant and support. [1] J. Millerioux, C. Cruz, A. Bazire, V. Polly, G. Lallement, L. Lefeuvre, D. Josse, Toxicol. In Vitro, 2009, 23, 127-133. [2] O. Koper, K.J. Klabunde, US Patent WO 01/78506 A1 2001. [3] A. Saxena, A.K. Srivastava, B. Singh, A. Goyal, J. Hazard. Mater., 2012, 211-212, 226-232. [4] O. Oddes, S. Amigoni, E. Taffin de Givenchy, P. Reeve, Y. Duccini, F. Guittard, J. Appl. Polym. Sci. 2011, 120, 2685-2692. [5] L. Clément, A. Zenerino, C. Hurel, S. Amigoni, E. Taffin de Givenchy, F. Guittard, N. Marmier, accepted in Science of the Total Environment. 16:00 Targeting of Gd nanoparticles for amyloidosis diagnosis Authors : P. Mowat (1), M. Plissonneau (2), N. Stransky-Heilkron (3), E. Allémann (3), X. Montet (3), M. Dumoulin (4), C. Louis (5), F. Lux (2), O. Tillement (2), C. Marquette (1), V. Forge (1) Affiliations : (1) Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), UMR 5620, Université Lyon 1, France; (2) Laboratoire de Chimie et Biologie des Métaux (CBM, AFFOND), UMR 5249, CEA Grenoble, France; (3) School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland; (4) Centre d ingénierie des protéines, Université de Liège, Belgique; (5) Nano-H SAS, Saint Quentin-Fallavier, France Resume : The challenge of this work is to detect, at an early time, amyloid fibrils which form and accumulate in the extracellular space of pathological tissues (Alzheimer, type 2 diabetes) in order to apply a therapy before irreversible alterations of organs [1]. For this, a new type of gadolinium nanoparticles (mean size of 5 nm) functionalized with peptides or with camelid antibody fragments (nanobodies, [2]) is developed. The Gd nanoparticles (Aguix ) are composed of a polysiloxane matrix with 7 Gd-DOTA grafted on the silica for subsequent MRI detection. Two other imaging techniques (fluorescence, scintigraphy) can be performed with the particles when incorporating organic dyes (FITC, RBITC, cy5) on the polysiloxane structure and radioisotopes (99mTc, 111In) in the free DOTA cycles. These multimodal nanoparticles display an appropriate biodistribution with no undesirable uptake in organs and are excreted by renal route. Their blood circulating time is longer than the one of classical molecular contrast agents [3]. Two kinds of amyloid deposits are considered for targeting: IAPP (Islet Amyloid PolyPeptide) fibrils present in the type-ii diabetes and TTR (Transthyretin) fibrils present in a lot of organs and responsible for several diseases (polyneuropathy, cardiomyopathy). Designed hexapeptides, β sheet structures existing in IAPP and TTR deposits are covalently linked on amino groups of the polysiloxane matrix and are able to bind specifically to fibrils. B10 camelid nanobodies are able to recognize an amyloid specific conformational epitope. We succeeded to synthesize both types of fibrils: IAPP (diabetes) and TTR (polyneuropathy). An original method for a peptide assay in NPs solutions was set up by circular dichroism and promising in vitro results of binding NPs-peptides with fibrils were also obtained using biophysical methods (fluorescence anisotropy, FRET). In vivo studies on a TTR rat model will be started shortly in collaboration with a Portuguese team (MJ. Saraiva, Institute of Molecular and Cellular Biology, Porto) as well as a study on transgenic mice expressing human IAPP in collaboration with a Swiss team (E. Allémann, X. Montet, University of Geneva). [1] A. Chenal et al. (2011) Amyloid fibrils formed by the programmed cell death regulator Bcl-xL. J Mol Biol 415, 584-99. [2] M. Dumoulin and C. M. Dobson. (2004) Probing the origins, diagnosis and treatment of amyloid diseases using antibodies. Biochimie 86, 589-600 (review) [3] F. Lux et al. (2011) Ultrasmall Rigid Particles as Multimodal Probes for Medical Applications. Angewandte Chemistry International Edition 50, 12299-12303. 16:00 Monodisperse oil core silica nanoshell as promising tool for nanomedicine Authors : Raffaele Vecchione*, Giuseppina Luciani** ***, Vincenzo Calcagno***, Anshuman Jakhmola*, Brigida Silvestri**, Aniello Costantini**, Francesco Branda** ***, Paolo Antonio Netti* ** *** Affiliations : * Istituto Italiano di Tecnologia, IIT@CRIB, Largo Barsanti e Matteucci, 53 80125 Napoli, Italy ** Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale, Universita di Napoli Federico II, Piazzale Tecchio, 80 80125 Napoli, Italy *** Centro di Ricerca Interdipartimentale sui Biomateriali CRIB, Università di Napoli Federico II, Piazzale Tecchio, 80 80125 Napoli, Italy Resume : Nanotechnology applied to medicine not only is gaining attention in the field of drug delivery but also as a potential platform for diagnostics. Nanocarriers can embed several tracers to track and image the fate of any nanomedicine from systemic to the subcellular level. Simultaneous imaging and drug delivery have already been demonstrated. One intriguing route is the use of a core shell structure which effectively allows protecting both drug and/or tracers in the inner core. Inorganic shells can be really impermeable, biocompatible and easy to functionalize 5 6

12 sur 30 06/05/2013 09:31 to guaranty active targeting as well as long circulation times. In this work silica nanocapsules have been successfully fabricated. The synthetic strategy of synthesis is a multi step process involving encapsulation of nanodroplets of oil in a bilayer of chitosan and heparin followed by deposition of silica controlled by varying the amount of TEOS. Silica nanostructures were checked by both DLS and morphological analysis such as SEM, TEM, AFM and in fluorescence microscopy (Confocal and STED). The hollow core which is oil may include a variety of materials like high payloads of hydrophobic drugs, as well as fluorescent quantum dots (QDs), magnetic or gold NPs, among various other variants for drug delivery and multi-modal imaging. In comparison with traditional materials, there are only a few articles on silica nanocapsules with oil core because of the difficulty in managing emulsions at nanoscale level with a stable oil template. Here we stabilize them simply by means of a polymer shell before silica shell preparation at room temperature and with water as solvent. In conclusion, monodisperse silica nanocapsules have been obtained with an environmentally friendly process as no high temperatures and ph are used. 16:00 Advances in gold nanoparticle radiosensitization mechanism Authors : Emilie Brun, Manon Gilles, Cécile Sicard-Roselli Affiliations : Laboratoire de Chimie Physique CNRS UMR 8000, Université Paris-Sud, 91405 Orsay, France Resume : Though radiotherapy is one of the predominant treatments against cancer, its efficiency is limited by induced toxicity to healthy tissues. To considerably increase damage to cancerous cells specifically, several experiments were performed during the last decade showing a significant radiosensitizing effect of nano-objects. This phenomenon has been established experimentally not only in vitro for plasmids and proteins, but also in cells and in vivo, for various kinds of nanoparticles and radiation qualities. Several mechanisms for damage enhancement have been proposed, but none of them is really convincing. In this presentation, we will illustrate this radiosensitization impact of gold nanoparticles and give some new advances on the basic mechanisms of the nanoparticles interaction with ionizing radiation. A better knowledge of the species produced should allow a more profitable use for biological and therapeutic applications. Brun, E., L. Sanche, and C. Sicard-Roselli, Coll. Surfaces B: Biointerfaces, 2009. 77(1): p. 128-134. Jain, S.; Coulter, J. A.; Hounsell, A. R.; Butterworth, K. T.;McMahon, S. J.; Hyland, W. B.; Muir, M. F.; Dickson, G. R.; Prise, K. M.;Currell, F. J.;O Sullivan, J. M.; Hirst, D. G. Int. J. Radiat. Oncol. Biol. Phys. 79 (2010), 531 Herold, D. M., Das, I. J., Stobbe, C. C., Iyer, R. V., and Chapman, J. D. (2000) Int. J. Radiat. Biol. 76, 1357-1364. Hainfeld, J. J., Slatkin, D. N., and Smilowitz, H. M. (2004) Phys. Med. Biol. 49, N309-N315 16:00 Modeling of local-field distributions at the silicon nanowires for its using as nerve prosthetics Authors : O.Ryabchykov, A.Klimovska, V.Lozovski, N.Vysotska Affiliations : Yu.Chaikovskyy, A.Korsak, V.Likhodievsky Resume : The study of nerve fibers reparation and development of methods that use silicon nanowires are topical today. Electromagnetic field facilitates reparation of nerve fibers. Theoretical approaches and mathematical modeling describe and predict the behavior of these silicon structures. We analyzed physical reasons of local field enhancement along silicon nanostructures by various methods. The task contained numerical and analytical calculations and strong theoretical base. Calculations are made for models with different external influences like IR irradiation. Green function method is used to find the field distribution around the nanowires. It shows possibility of correlation between local field distribution and nerve fibers recovery time. Parameters and conditions to form areas of high-intense field could be obtained in this model. FDTD method to verify analytic calculations for some parameters was used. The results of calculations allow us to suppose using the silicon nanowires as prosthesis of nerve fibers. The study of silicon nanowires as nerve fibers prosthesis was made in vivo when the mice were operated with prosthetics of sciatic nerve. Recovery of mice sciatic nerve show that proposed prosthetic method demonstrated rather good results. 16:00 SAFE AND EFFICIENT UNIFORM MAGNETIC NANOPARTICLES SYNTHESIZED BY AN IMPROVED AQUEOUS ROUTE WITH TAILORED SURFACE PROPERTIES Authors : Y. Luengo, C. Serrano, M. Calero, A. Villanueva, F. Herranz, P. de la Presa,, S. Veintemillas-Verdaguer, C. J. Serna, M. P. Morales Affiliations : Departamento de Biomateriales y Materiales Bioinspirados, Instituto de Ciencia de Materiales de Madrid/CSIC, Sor Juana Inés de la Cruz 3, Campus de Cantoblanco, Madrid 28049, Spain; Advanced Imaging Unit. Department of Epidemiology, Atherothrombosis and Imaging. Fundación Centro Nacional de Investigaciones 7 8 9

13 sur 30 06/05/2013 09:31 Cardiovasculares (CNIC). 28029 Madrid (Spain); Departamento de Biología, Universidad Autónoma de Madrid, Darwin 2, Cantoblanco, 28049 Madrid, Spain; Instituto de Magnetismo Aplicado (UCM-ADIF-CSIC), P.O. Box 155, Las Rozas, Madrid 28230, Spain; Departamento de Física de Materiales, Universidad Complutense de Madrid, Madrid, Spain. Resume : Here, we report a highly reproducible synthesis method in water of magnetite nanoparticles with sizes between 6 and 14 nm and standard deviations of 0.2. This procedure is a combination of the standard coprecipitation and an acid treatment that improves colloidal and magnetic properties through a series of partial dissolution-recrystallization steps [1]. Finally complete structural, colloidal and magnetic characterization of the samples has been carried out. To render long term colloidal stability at ph 7, hydrodynamic sizes bellow 100 nm and highly charged surfaces, particles were coated with (3-aminopropyl)-triethoxysilane (APS) and dimercaptosuccinic acid (DMSA), using procedures previously described [2]. Both surface modifications are capable of bonding different bioactive molecules and enhance cellular uptake. Nanoparticle cytocompatibility has been investigated in vitro with murine L929 fibroblasts, porcine endothelial progenitor cells and cancer cells by analyzing cellular uptake, viability and cell cycle. The possibility of following MNP biodistribution by MRI is assessed by means of the measured longitudinal and transversal relaxation times (T1 and T2) of the colloidal SPIO suspensions (r1 = 8,5 mm-1 s-1, r2 = 327,4 mm-1 s-1). Finally, heating efficiency of the particles under application of an external alternating magnetic field was evaluated from the Specific Absorption Rate (SAR) (58 W/gFe) [3]. REFERENCES [1] Costo et al., Langmuir 2012, 28, 178-185 [2] Mornet et al., J. Magn. Magn. Mater. 2005, 293, 127-134 [3] de la Presa et al., J. Phys. Chem. C 2012, 116, 25602-25610 16:00 Synthesis and Characterization of Silver Nanoparticles in Glass Ionomer Matrix for Dental Application Authors : Lilian PAIVA1, Luiz PEREIRA COSTA2, Rossana THIRÉ3, Lydie PLOUX1 Affiliations : 1Institut de Science des Matériaux de Mulhouse - IS2M/UHA, France ; 2 Universidade Tiradentes - UNIT, Brazil; 3 Universidade Federal do Rio de Janeiro - UFRJ, Brazil. Resume : Dental caries is affecting 60 90% of school children and nearly 100% of adults. Reducing bacterial adhesion on the surfaces of dental materials shall be decisive trend, specifically for glass ionomers cements (GIC), the most indicated material according to minimal invasive operative interventions. The aim of this study is to synthesize silver nanoparticles (AgNP) in GIC polymer content, expecting to attribute preventive bacterial adhesion properties to the material s surface, inherent to AgNP. Poly(acrylic acid) solutions (PAA) were used as reducing and stabilizing agent; AgNP synthesis was thus taken place in situ by a photochemical route. Silver nitrate and tartaric acid (TA) were added to PAA solution (average Mw 100.000 35% wt. in H2O). This synthesis route was selected in order to mimic solutions used for dental purposes, without adding any substance that would change cement mechanical and kinetic properties. Solutions were UV irradiated ranging from 5 to 60 min. Size and distribution of AgNP were characterized by visible and ultraviolet spectroscopy and transmission electron microscopy (TEM). Solutions with TA irradiated for 10 min contained AgNP sized about 40 nm and apparently less aggregated than solutions irradiated for longer time. It was thus concluded that synthesis of AgNP at the GIC matrix components is feasible and potentially applicable without changing important properties of GIC. In vitro biological evaluation is under investigation. 16:00 Pegylated Biodegradable Nanoparticles for Paclitaxel Delivery Authors : Claudio Colombo, Massimo Zucchetti, Lavinia Morosi, Massimo Morbidelli, Davide Moscatelli Affiliations : Claudio Colombo, Davide Moscatelli, Politecnico di Milano, Milan Italy; Massimo Zucchetti, Lavinia Morosi, Mario Negri Institute for Pharmacological Research, Milan, Italy; Massimo Morbidelli, ETH Zurich, Zurich, Switzerland; Resume : In this work nanoparticles (NPs) based on comb-like polymers composed by poly caprolactone (PCL), poly lactic acid (PLA) and poly ethylene glycol (PEG) branches have been synthetized. By changing the molecular weight and the composition of these polymers the degradation behavior of the obtained NPs (tested in cell medium) has been tuned from few hours up to months. Paclitaxel has been loaded into the NPs through and emulsion-evaporation process consisting in the incubation of NPs latexes concentrated under vacuum with a solution of paclitaxel in ethanol. A loading efficiency of about 50% was determined via HPLC measurements while the free drug was removed by dialysis. The biodistribution of the paclitaxel loaded NPs was studied in mice bearing breast cancer (4T1 line cells) using nanoparticles with different dimensions and compositions. The influence of NPs characteristics on the overall biodistribution has been studied, in particular in the tumor. 10 11

14 sur 30 06/05/2013 09:31 16:00 Biodegradable and Biocompatible Comb-Like Polymers for Biomedical Applications Authors : Davide Moscatelli, Massimo Morbidelli Affiliations : Davide Moscatelli, Politecnico di Milano, Milan, Italy Massimo Morbidelli, ETH Zurich, Switzerland Resume : Polyesters have a strong and increasing importance in material science due to their biocompatibility and biodegradability that make these materials attractive for biological uses, nowadays mainly devoted to drug delivery applications, such as nanoparticles (NPs). In this work biocompatible and biodegradable NPs, with tunable hydrophobicity and biodegradation kinetics, were synthesized using novel Comb-Like Polymers (CLB). The synthesis and characterization of both polymers and NPs based on PLA, PCL and PLGA is detailed. The proposed NPs synthesis allows obtaining small and better controlled particle sizes than current synthetic methods such as nanoprecipitation which, in addition, involves the use of an organic solvent. Moreover using this process it is relatively easy to tune final nanoparticles features: influence of parameters such as emulsifier type, feeding mode and macromonomer chain length has been investigated. In addition, comb-like polymer obtained through the copolymerization of these novel macromonomers with pegylated hydroxyethylmethacrylate monomers (HEMA-PEG) have been produced through a surfactant free polymerization process. Produced NPs satisfy requirements for biological purpose for intravenous drug delivery in terms of size, particle size distribution, biodegradability and biocompatibility. Finally, results obtained for imaging, cell tracking (stem cells), and toxicity studies are reported. 16:00 FUNCTIONALIZATION OF MAGNETIC IRON NANOPARTICLES WITH TETRAPHOSPHONATE CAVITAND AND PEG VIA CLICK CHEMISTRY FOR BIOMEDICAL APPLICATION Authors : C. Tudisco1, F. Bertani2, E. Dalcanale2, M. T. Cambria1, G. G. Condorelli1 Affiliations : 1 Dipartimento di Scienze Chimiche, Università di Catania and INSTM UdR di Catania, v.le A. Doria 6, 95125 Catania, Italy; 2 Dipartimento di Chimica Organica e Industriale, Università di Parma and INSTM UdR di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy Resume : Functionalized magnetic iron nanoparticles (MNPs) are promising tools for advanced medical applications such as MRI, hyperthermia, drug delivery etc. In most of their potential applications, the hybrid organic/inorganic nature of the surface plays a pivotal role in determining their properties. In this context, clickchemistry is an efficient method to bond functional molecules for the engineering of NP surfaces. In this contribution, MNPs have been functionalized with tetraphosphonate cavitand receptors (Tiiii), proved able to complex N-monomethylated species with high selectivity,1 and polyethylene glicol (PEG) via click-chemistry reaction. The grafting process is based on MNPs prefunctionalization with a bifunctional phosphonic linker, 10-undecynylphosphonic acid, able to anchoring on iron surface through the phosphonic group. The Tiiii cavitand and the PEG modified with azide moieties have been then bonded to the resulting alkynefunctionalized MNPs through a click reaction. Each reaction step has been monitored by using X-ray photoelectron and FTIR spectroscopies. Tiiii functionalized MNPs have been able to complex N-methyl ammonium derivatives, such as, sarcosine a biomarker for prostate cancer, neurotrasmitters and N-methylated antitumoral drugs. Further the introduction of PEG moieties promoted biocompatibility of functionalized MNPs, thus allowing their use in biological environmental. 1.R. Pinalli, E. Dalcanale Acc. Chem. Res. DOI10.1021/ar300178m 16:00 Engineering of biodegradable polymeric nanoparticles for drug delivery Authors : A. Repanas1, V. Karagkiozaki1, D. G. Fatouros2, P. Karagiannidis1, S. Logothetidis1 Affiliations : 1. Νanomedicine Group, Department of Physics, Lab for Thin Films -Nanosystems & Nanometrology, Aristotle University of Thessaloniki, Greece 2. Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Greece Resume : Biodegradable polymeric nanoparticles (BNPs) provide new means of drug delivery as they gradually degrade inside the host organism releasing specific amount of drug in a controllable way. These drug eluting BNPs can be of use in stents in order to inhibit thrombosis while at the same time minimizing inflammation, caused by immune system responses of the host. Herein, we designed and synthesized BNPs loaded with the anti-platelet drug dipyridamole, by nanoprecipitation method. Poly (DL-lactide-co-glycolide) (PLGA), was used to form NPs in a solution containing 1% w/v polyethylene glycol (PEG). The engineered BNPs were loaded with different amounts of dipyridamole. Then, they were separated from the free drug by appropriate centrifugation, and re-dispersed in 12 13 14

15 sur 30 06/05/2013 09:31 solution containing 0.2% w/v bovine serum albumin (BSA). PEG and BSA were selected to reduce the immunotoxicity of the NPs. The morphology, size and electrokinetic properties of plain and drug loaded NPs were investigated by Atomic Force Microscopy (AFM), dynamic light scattering (DLS) and ζ-potential studies, respectively. The size of drug loaded particles in the dispersion was influenced by drug proportion, with an increase in drug content of the dispersion resulting in decreased drug particle size. Consistent with the presence of the drug onto the surface of NPs, the ζ-potential values of loaded NPs were lower (in absolute values) compared with plain ones. Moreover, the presence of PEG 2000 and BSA in the aqueous phase induced changes to the physicochemical properties of the particles as witnessed by the measured surface charge and the size diameter values. The results justify further investigation of the suitability of the PLGA modified NPs for cardiovascular applications. 16:00 Design and characterization of photoactive carbon tubes functionalized by the Cu organic complex histidine as biomedical nanoparticles Authors : Olena Kysil[a], Liliana Lukashuk[a], Oleksandr Ivaniuta[a], Oleksii Dubok[a], Eugenia Buzaneva[a], Uwe Ritter[b], Peter Scharff[b] Affiliations : a Taras Shevchenko National University of Kyiv, Departments of Medical Radiophysics and Inorganic Chemistry, Volodymyrska Str. 64/13, 01601 Kyiv, Ukraine c Ilmenau University of Technology, Institute of Chemistry and Biotechnology, 98684, Ilmenau, Germany, PF 100565 emrs@univ.kiev.ua Resume : The design concept to create photoactive carbon tubes biohybrides is based on constructed molecular models for the photoemission of semiconductor carbon nanotubes (CNTs) functionalized by attached to the core and ends photoactive molecular complexes: metal (d - transition metal Cu) - organic (azole ligand) complex or by this complex with coordinative bonded biomolecule (histidine). This idea is based on potential applications of photoactive carbon tubes with attached biomolecules as biomedical nanoparticles: nanophotomarker, drug delivery nanosystem [1]. The characterization of these tubes by the IR spectroscopy was carried out using the samples from carbon nanotubes nanostructures organized due to bonds between the metal ions and the ligands or the histidine molecules at different tubes into suspensions. The architecture (SEM images) and the photoemission (PL spectroscopy) for nanostructures from these functionalized CNT s in adsorbed layer at silicon substrate are characterized. The SEM images for this layer are interpreted using proposed molecular architectures models for single tubes connected through Cu 2+ with attached two ligands molecules at different tubes cores and these bonds are partially retain in the complexes with coordinative bonded histedine molecules that can decrease formation of these structures due to their adsorbing on tubes. These nanostructures with namely one and both two types bonds between single tubes are characterized by photoemission wide bands, having different intensities and different three subbands in visible range. Differences between spectra are interpreted as the organization added donor accepter pairs in carbon tubes biohybrides including histedine molecules. Biocompatibility of the carbon tubes biohybrides is determined by histidine covering the tube wall. This work is defined by the scientific program on Modeling and complex investigations of multifunctional molecular nanostructures: integrated nanocarbon, biological and organic polymer molecules. [1]. M.S. Digge, R.S. Moon, S.G. Gattani, Application of Carbon Nanotubes in Drug Delivery: A Review, Int. J. PharmTech Res., 2012, 4, 2, 839 16:00 Design of gold nanoparticles for radiotherapy using Monte Carlo simulations of secondary X-rays and electrons Authors : Bert De Roo1, Mattias Vervaele1, Rüveyda Dok2, Cédric Spaas1, Sandra Nuyts2, Frank Vandenheuvel2, Jean-Pierre Locquet1 Affiliations : 1 Department of Physics and Astronomy, KU Leuven, Leuven, Belgium 2 Department of Oncology, KU Leuven, Leuven, Belgium Resume : The addition of gold nanoparticles offers a new approach to enhance the effectiveness of radiation in low energy X-ray therapy. To find the optimal parameters (size, distribution) under which gold nanoparticles adsorb low energy X-rays (20-100keV) and re-emit electrons and X-rays, Monte-Carlo simulations were performed using GEANT4. In these simulations we took into account not only the secondary electrons but also the secondary gamma rays. In this way we could see a significant increase in deposited energy further away (up to more than 50um) compared to recent papers. This increase in deposited energy was proportional with the square of radius of the NP and mainly due to secondary X-rays. The dose enhancement is maximal very close to the nanoparticle (a few 1000) and is still large (a factor 30) at 50um away from the nanoparticle for a 10nm diameter gold nanoparticle irradiated with a photon beam of 20 kev. We investigated the X-ray self-absorption of nanoparticles and found that this was significant lowered (~20%) 15 16

16 sur 30 06/05/2013 09:31 -compared to literature values- due to the fact that secondary X-rays are now properly taken into account. Furthermore different geometric shapes are explored to see which one is the most efficient for use in gold nanoparticle aided radiotherapy. Finally in order to test these predictions, nanoparticles are currently tested ex vitro and in vitro (in SQD9 head and neck cencer cells) in combination with low energy radiation therapy. 16:00 UV-VIS analysis of gold nanoparticle formation and aging Authors : Bert De Roo1, Olivier Deruyver1, Amina Tijani-Wirth1, Jin Won Seo2 and Jean-Pierre Locquet1 Affiliations : Department of Physics and Astronomy, KU Leuven, Leuven, Belgium Department of Metallurgy and Materials Engineering, KU Leuven, Leuven, Belgium Resume : For biomedical applications, it's imperative that the used nanoparticles remain stable in solution before they are used. In this work, gold nanoparticles of various diameters (12-25nm) were synthesized to study their stability and size. Calculations were done to correlate the UV-VIS spectra with the diameter of the nanoparticles via the absorbance ratio at 450 nm (A450) and the absorbance at the surface plasmon resonance (Aspr). We found out that the correlation was double exponential in the region of 5-30nm (R²>99.9%). Transmission electron microscopy images (analyzed with ImageJ to obtain the size of nanoparticles) were used to correlate the obtained UV-VIS spectra with the fit of a double exponential (R²>95%). First we used the citrate reduction method to study how the formation of these nanoparticles completes over a time scale between 30 and 330 seconds. This lead to the conclusion that first small seed nanoparticles are formed (5nm) which then condensate into big particles (50nm) and that they are completely formed after 330 seconds. Second, such nanoparticles were then used to follow their aging over a time scale up to 4 weeks. These results enable to monitor how these nanoparticles grow/aggregate over time. We found a linear relation between time and the A450/Aspr ratio with an R² up to more than 99%. This study demonstrates that the aging process can be followed on UV-VIS spectra without relying on expensive and time-consuming equipment. 16:00 Preparation and characterization of magneto-sensitive silica nanoparticles with hydrophobic and hydrophilic/hydrophobic surface layer Authors : V.V.Tomina, I.V.Melnyk, Yu.L.Zub Affiliations : Chuiko Institute of Surface Chemistry of NASof Ukraine, 17 General Naumov Street, Kyiv 03164, Ukraine Resume : The current research is focused on the synthesis and characterization of functionalized magnetic nanoparticles for sorption of organic and biological substances. Earlier, the attempts have been made to create bifunctional silica microspheres with hydrophilic (amino) and hydrophobic (alkyl: methyl or propyl) functional groups for human serum albumin sorption [1]. In order simplify their practical application, there was introduced magneto-sensitive core based on Fe3O4. Magneto-sensitive functionalized particles form stable suspensions in the solutions and can be easily removed from them with the help of magnets. The introduction of hydrophobic surface groups prevents hydrogen bonds formation between functional (amino) groups, and promotes proteins sorption via non-specific hydrophobic interaction with protein molecules. As functional groups with hydrophobic properties there were used fluor-containing groups, which were introduced in the silica coating using 3,3,3-trifluoropropyltrimethoxysilane and 1H,1H,2H,2Hperfluorooctyltriethoxysilane as functionalizing agents. As hydrophilic groups, there were also used thiol groups along with amino groups. [1] I.V.Melnyk, Y.L. Zub // Microporous and Mesoporous Materials 2012 (154) p.196 16:00 IRON-OXIDE CORE/SHELL/ADSORPTION-SHELL NANOPARTICLE THIN COATINGS FABRICATED BY MAPLE FOR BIOLOGICAL APPLICATIONS Authors : R. Cristescu1, G. Dorcioman1, C. Popescu1, G. Socol1, I.N. Mihailescu1, D. Mihaiescu2, A. Grumezescu2, M. Enculescu3, C. Chifiriuc4, C Bleotu4,5, and D. B. Chrisey6 Affiliations : 1National Institute for Lasers, Plasma & Radiation Physics, Lasers Department, P.O.Box MG-36, Bucharest-Magurele, Romania 2Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, 1 7 Polizu Street, 011061 Bucharest, Romania 3National Institute of Materials Physics, P.O. Box MG-7, Bucharest-Magurele, Romania 4Faculty of Biology, University of Bucharest, Microbiology Immunology Department, 77206- Bucharest, Romania 5Stefan S Nicolau Institute of Virology, Bucharest, Romania 6Department of Physics and Engineering Physics, Tulane University, New Orleans, LA, USA Resume : Potential applications of core/shell nanoparticles geometries arise from their capability to display properties that neither of the individual materials could exhibit. This research is focused on functionalized Fe3O4 core/shell/adsorption-shell nanoparticles assembled thin coatings fabricated by matrix assisted pulsed laser evaporation (MAPLE), as vehicle focused to antibacterial drugs targeted delivery. 17 18 19

17 sur 30 06/05/2013 09:31 Thin coating systems were characterized by FTIR, SEM, TEM, XRD, and investigated by in vitro biological assays, using Gram negative and Gram positive bacterial reference strains, for establishing their antimicrobial activityas well as eukaryotic cells for cytotoxicity assays. Higher laser fluencies resulted in thin films degradation, whereas lower fluencies (~200 mj/cm2) produced thin films with a chemical structure similar to the starting material. SEM micrographs revealed a uniform morphology of the composite nanoparticles, while TEM investigations evidenced 2-20 nm Fe3O4 core nanoparticle diameters. The antibiotic charged nanoparticles influenced the cellular viability, as well as the microbial and eukaryotic cells adherence to the inert substrate. We concluded that iron oxide nanoparticles could be used for the development of novel antimicrobial materials or strategies for preventing the microbial adherence and further development of medical biofilms formed by different pathogenic agents, frequently implicated in the etiology of chronic and hard to treat infections. 16:00 In vitro characterization and quantification of PEGylated magnetic iron oxide nanoparticles using anti polyethylen glycol monoclonal antibodies Authors : A. Ruiz (1,2), M. Martín (3), M.P. Morales (1), L. Kremer (3)* Affiliations : 1 Departamento de Biomateriales y Materiales Bioinspirados, Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Cantoblanco, 28049 Madrid, Spain; 2 Centro de Estudios Avanzados de Cuba, San Antonio de Los Baños km 3½, La Habana, Cuba; 3 Departamento de Herramientas Proteicas, Centro Nacional de Biotecnologia, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain. Resume : Polyethylene glycol (PEG) coated magnetic iron oxide nanoparticles (MNP) are widely used for different biomedical applications, including Magnetic Resonance Imaging (MRI) and iron anemia treatments. Each MNP biocompatibility is linked to the intrinsic toxicity of the MNP core and coating, cell/tissue biodistribution, clearance and metabolization. To assess the MNP biosafety, technologies capable of detecting them traveling in the bloodstream or in other parts of the body are required. Here we describe the preparation of PEGylated nanoparticles of 12 nm in diameter and ~50 nm of hydrodynamic size obtained by thermal decomposition in organic media. Ligand exchange reaction with dimercaptosuccinic acid (DMSA) and amine polyethylene glycol derivatives coupling via carbodiimide (EDC)-mediated reaction, have been done following a protocol recently developed in our lab. The reaction proceeds by formation of an amide bond by a nucleophilic substitution, with EDC as an activator of the carboxyl group. We have developed an anti-peg sandwich ELISA test that allows detection of PEGylated nanoparticles by direct binding to PEG regardless of the complexity of the media. An anti-peg monoclonal antibody (mab), PEG02, is used both as capture and detection agent allowing the sensitive detection of MNP, even those coated with short chain PEG (2000 Da). Under these conditions, detection limits of PEG conjugated to MNP as low as 2.4 pg/ml have been achieved. Moreover, MNP intraperitoneally administrated in a mouse model were detected in plasma through its PEG content by this ELISA test. Results were compared to iron concentration by elemental analysis (ICP = inductively coupled plasma). Ex vivo analyses of plasma samples containing PEG (20000 Da) conjugated nanoparticles showed a detection limit of approximately 25 ng, which is several orders of magnitude more sensitive than other analytical methods (HPLC, colorimetric) and more easy and safety than radiolabeling techniques. 16:00 SMART NANOPARTICLES FOR CANCER FIGHT Authors : Francesco Branda*, Aniello Costantini*, Giuseppina Lucianii*, Brigida Silvestri*, Daniela Guarnieri^, Paolo Antonio Netti*^ Affiliations : *Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale University of Naples Federico II, Naples, Italy; ^Center for Advanced Biomaterials for Health Care@CRIB, Istituto Italiano di Tecnologia and Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy Resume : A large number of recent literature data focus on modification/modulation of surface chemistry of inorganic materials in order to improve their functional properties. Here we report the use of a chimie douce approch, the sol-gel route, to prepare novel hybrid nanostructures based on silica nanoparticles: folate decorated/doxorubicin charged PEGylated silica nanoparticles (DOX FA PEG SiO2 NPs) and heparin conjugated silica nanoparticles (HEP SiO2 NPs) Pegylation avoids the undesired interactions with the immune system. Folate decoration improves selective internalization in some cancer cells, by receptor mediated endocytosis. Heparin (H), low molecular weight heparin (LMWH) and some chemically modified species of heparin (MH) were recognised as both anti-angiogenesis agents and vectors able to bind protein and enzymes overexpressed in the tumour microenvironment. Both doxorubicin charged/folate decoration and heparin conjugation to silica nanoparticles are expected to impart to 20 21

18 sur 30 06/05/2013 09:31 silica nanocarrier both targeting and therapeutic very effective properties. Morphological analysis (SEM, TEM) shows, in both cases, monodispersed spherical nanoparticles about 100nm in diameter. Heparin/silica weight ratio was evaluated to be 0.61. The encapsulation efficiency of DOX FA PEG SiO2 NPs [EE = (DOXentrapped / DOX total) x100] was quantified to be 32%; cytotoxicity assay proved that the bond to the NP does not reduce the doxorubicin therapeutic efficacy. 16:00 A NANOPLATFORM BASED ON SILICA CORE-SHELL NANOPARTICLES AND BODIPY COPPER SENSOR FOR MONITORING INTRACELLULAR DYNAMICS OF COPPER TRAFFICKING Authors : Cristina Satriano (1*), Maria Laura Giuffrida (2), Agata Copani (3), Giuseppe Trusso (1), Gaetano Tomaselli (1), Enrico Rampazzo (4), Damiano Genovese (4), Massimo Sgarzi (4), Luca Prodi (4), Enrico Rizzarelli (1) Affiliations : (1) Department of Chemical Sciences, Catania University, Catania, Italy; (2) Department of Pharmaceutical Sciences, Catania University, Catania, Italy; (3) Institute of Biostructures and Bioimages, National Council of Research, Catania, Italy; (4) Department of Chemistry G. Ciamician, Bologna University, Bologna, Italy. Resume : Spatio-temporal changes in intracellular copper have known to affect the tiny borderline between physiological and pathological aspects [1]. We present here a nanoparticle-based strategy to detect intracellular copper distribution and to follow its dynamic changes upon several cell perturbation. A fluorescent probe consisting of porous silica nanoparticles dye-doped in the core with coumarin molecules and functionalized on the outer shell with a bodipy-containing copper chemosensor, was employed as highly efficient transduction nanoplatform for intracellular copper detection due both to energy transfer process and to a high affinity and specificity to bind monovalent copper [2]. The systematic investigation of fluorescence intensity as well as co-localization with respect to several sub-cellular districts was carried out on neuroblastoma cells as function of several parameters, including the cellular state (differentiated or not), buffer, ph, peptides addition, copper deprivation/supplementation. Results demonstrate the enhanced imaging capability of the nanoparticle-based sensor compared with the traditional free chemosensor, as well as highlight the potential use of the new system as multifunctional nanoplatform for both imaging and drug delivery applications [3]. [1] Neurodegeneration: metallostasis and proteostasis D. Milardi and E. Rizzarelli (Ed). RSC, 2011. [2] E. Rampazzo et al. Chem. Eur. J. 2011, 17, 13429. [3] E. Rampazzo et al. Nanoscale, 2012, 4, 824. 16:00 In vitro release and cytotoxicity in 2D and 3D of sub-100 nm PLGA-PEG nanoparticles Authors : Marco Biondi, Daniela Guarnieri, Hui Yu, Valentina Belli, Paolo Antonio Netti Affiliations : Marco Biondi: Dipartimento di Chimica Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, Napoli, Italy. Centro di Ricerca Interdipartimentale sui Biomateriali (CRIB), Università di Napoli Federico II, Piazzale Tecchio 80, Napoli, Italy. Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Daniela Guarnieri: Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Hui Yu: Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Valentina Belli: Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Paolo Antonio Netti: Centro di Ricerca Interdipartimentale sui Biomateriali (CRIB), Università di Napoli Federico II, Piazzale Tecchio 80, Napoli, Italy. Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy. Dipartimento di Ingegneria dei Materiali e della Produzione, Università di Napoli Federico II, Piazzale Tecchio 80, Napoli, Italy. Resume : Enhanced tumor penetration is considered fundamental to improve chemotherapy efficacy since it directly influences nanoparticle (NP) cell uptake. In this perspective, size reduction of NPs taking advantage of the enhanced permeability and retention (EPR) effect is a very challenging task. Thus, the aims of this study were: (i) the engineering of < 100 nm biodegradable NPs, made up of a poly(d,l-lactic-co-glycolic acid) (PLGA) block poly(ethylene glycol) (PEG) (namely PEGA) copolymer, and loaded with doxorubicin (Dox); (ii) the translation of standard 2D cytotoxicity studies to 3D collagen model systems in which an initial step gradient of NPs/Dox was imposed. Depending on the formulation/size of the NPs and on the ph of the release medium, Dox release could be prolonged for days to weeks. Results clearly showed that sub - 100 nm NPs were effectively internalized by HeLa cells in 2D and were less cytotoxic compared to the free drug. In 3D, < 100 nm NPs were significantly more toxic than compared to bigger ones towards HeLa cells. We found that cell death rate was clearly affected by the contributions of drug release and device transport through collagen. Taken all 22 23

19 sur 30 06/05/2013 09:31 together, results showed the importance of NP size reduction as a fundamental feature from both a technological and biological point of view. 16:00 Microwave Synthesis of Cobalt Ferrite Authors : Niall Maclean(a),(b), Nguyen T K Thanha,(b)*, Shinya Maenosono(c) Affiliations : (a)university College London, Gower street, London, WC1E 6BT, United Kingdom. (b)the Royal Institution of Great Britain, 21 Albemarle street, London, W1S 4BS, United Kingdom. (c)japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan. *ntk.thanh@ucl.ac.uk, www.ntk-thanh.co.uk Resume : Magnetic nanoparticles are very versatile and have been shown to be effective for magnetic drug delivery, hyperthermia cancer treatment and magnetic particle imaging [1]. Currently the leading material within the field is magnetite, Fe3O4, which has FDA approval; however, this material is not univerally applicable as it does not have a noteable magnetic anisotrpy. Cobalt ferrite, CoFe2O4, is a similar inverse spinel structure to that of magnetite and due to the presence of the cobalt has a magnetic anisotropy, 1.8-3.0 106 ergs/cm3, which can make the material better suited for biomedical applications[2]. Wet chemical synthesies using a microwave heater have shown promise in producing nanoparticles of a high quality and excellent magnetic properties[3]. This synthesis of CoFe2O4 was carried out using a coprecipitation method of synthesis. We plan to carry out the thermal decomposition of iron and cobalt acetylacetatonates within a mircowave in an attempt to improve the size distribution, crystallinity and magnetic properties of the CoFe2O4. [1] Thanh, N.T.K. Magnetic Nanoparticles: from Fabrication to Clinical Applications. CRC Press, Taylor and Francis, (2012). [2] Tung, L.D., Kolesnichenko, V., Caruntu, D., Chou, N.H., O Connor, C.J., and Spinu, L. Journal of Applied Physics 93(10), 7486 (2003). [3] Bensebaa, F., Zavakuiche, F., L Ecuyer, P., Cochrane, R.W., Veres, T. Journal of Colloid and Interface Science 227(1) 104-110 (2004) 16:00 BOVINE EMBRYO DEVELOPMENT IN VITRO: A SENSITIVE ASSAY TO EVALUATE PLGA/PEG-NANOPARTICLES TOXICITY. Authors : Fiorentino I, Gualtieri R, Barbato V, Mollo V, Braun S, Netti P*, Guarnieri D*, Fusco S* and Talevi R. Contact author, Fiorentino I Affiliations : Dip. Biologia Strutturale e Funzionale Via Cinthia, Napoli Italy *Dip. Ingegneria dei Materiali e della Produzione -Piazzale Tecchio, Napoli Italy Resume : The heterogeneity of nanoparticles (NPs) developed for biomedical use emphasizes the need of sensitive toxicity tests. Data on somatic cells were conflictual and only a few studies were done on extremely sensitive processes such as embryo development. Herein we studied the toxicity of biodegradable 65nm poly(d,l-lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) NPs on bovine in vitro embryo development. Groups of 50 oocytes matured and fertilized in vitro, were cultured in SOFaa 5% FCS with rhodaminated NPs (10 or 50μg/mL) or vehicle for 8 days. Cleavage and 8 cell embryos were scored at day 3; blastocyst rates at day 8. Blastocysts were fixed, and 1) analysed to determine mean cell numbers (MCN) and NP internalization; 2) subjected to TUNEL to evaluate DNA fragmentation; 3) processed for ultrastructure. NPs at 50, and not at 10μg/mL, reduced the 8 cell embryo and blastocyst rates (treated vs control: 8 cell, 40 vs 60%, P<0,05; blastocyst, 34 vs 46,6%, P<0,05) but did not affect MCN and DNA fragmentation (treated vs control: MCN, 134± 40 vs 132±65; DNA fragmentation, 7,06%± 3,44 vs 7,09%±4,14). Confocal and TEM analysis showed that NPs were efficiently internalized and localized in cytoplasmic vacuoles and vesicles. In conclusion, PLGA-PEG-NPs exert a cytotoxic effect on embryo development in a dose-dependent manner. In vitro embryo development in animal models may represent a sensitive and appropriate assay of NP toxicity before their application in biomedicine. 16:00 Electrochemical Synthesis of ZnO-based Bioactive Nanomaterials Authors : R.A. Picca *1, A. Luciano 1, M.C. Sportelli 1, M.A. Nitti 2, N. Cioffi 1, L. Sabbatini 1 Affiliations : 1 Chemistry Department, Università degli Studi di Bari Aldo Moro Italy; 2 Physics Department M. Merlin, Università degli Studi di Bari Aldo Moro, Italy Resume : Bacterial growth prevention represents a key issue due to the spread of antibiotic resistant strains of various microorganisms. Among antibacterial nanomaterials, nanostructured ZnO has received great attention thanks to its bioactivity, stability and low toxicity [1]. Here we report a novel electrosynthetic approach to ZnO-based materials. Electrochemical methods for the synthesis of ZnO nanoparticles are still slightly exploited and are generally related to nanoparticle electrodeposition. ZnO particles are electrosynthesized in an alkaline aqueous medium in the presence of proper capping agents. Sodium dodecyl sulphate and cetyltrimethylammonium bromide (well-known surfactants) were employed for controlling particle morphology. Calcination process was carried out 24 25 26

20 sur 30 06/05/2013 09:31 to evaluate the influence of a thermal treatment on nanomaterial stoichiometry and structure. The influence of cationic/anionic agents on particle growth and shape is investigated by comparison with literature reporting the synthesis in the absence of surfactants [2]. TEM characterization, XPS, IR analyses and preliminary bioactivity tests will be presented to assess particle size distribution and their chemical and antibacterial properties. [1] N. Cioffi, M. Rai Eds., Nano-antimicrobials. Progress and Prospects. Springer-Verlag, Berlin Heidelberg (2012). [2] K.G. Chandrappa et al., J. Nanopart. Res. 12 (2010) 2667. Financial support from Italian MIUR Project PON01_02210 16:00 Design, synthesis and characterization of the Yb doped HAp magnetic and photoluminescent nanoparticles Authors : Oleksii Dubok1*, Oleksandr Shynkaruk2, Olena Kysil1, Eugenia Buzaneva1 Affiliations : 1 Taras Shevchenko National University of Kyiv, Volodymyrska str. 64/13, 01601 Kyiv, Ukraine 2Institute for Problems of Material Sciense NASU, Kryzhanivskogo str.3, 03142, Kyiv, Ukraine Resume : In order to design and to synthesis magnetic and photoluminescent nanoparticles from biomaterials hydrohyapaptite (HAp), which is known to be biocompatible, multifunctional and to have many biomedical applications, we considered that the unique biological properties of this material could be changed by different types of doping therefore we analyzed these the effectiveness of these methods. Experimentally several methods of synthesis of the HAр doped using oxides of ytterbium have been tested and compared. In results for the HAp synthesized nanoparticles substitution of only 2.3 % of calcium atoms by ytterbium resulted in twofold improving of magnetic and PL parameters without noticeable changes in biological properties. Study of FTIR, XPS and X-ray diffraction spectra of HAp nanoparticles doped with different CONTENT of ytterbium oxide demonstrated the possibility of formation of homogeneous solid solutions with ytterbium ion entering into HAP lattice mainly as Yb3+. Then doping with Yb of thе HAp nanoparticles expanded their use in biomedicine. In fact, the НАр nanoparticles can be used as a window created by nature for a dialogue with the inner world of living organisms, testing, correction and restoration of many capture therapy with the the HAp s bioceramics etc. This material is used to fill the bone defects and to stimulate the bone restoration in various fields of surgery. Now only the doped ceramics should provide the control of biotransformation process in vivo without biopsy due to achievement of high resolultion in X-ray and MRI bioimages. 16:00 ANALYSIS OF HYBRID COMPOUNDS IN NANOSENSORS FOR BIOMEDICAL APPLICATIONS Authors : L. Draghiciu, T. Ignat, A. Dinescu, M. Carp, M. Danila R. Muller Affiliations : National Institute for R&D in Microtechnologies -IMT-Bucharest Resume : Magnetic nanoparticles and serum albumina have been studied in biomedicine because of their potential applications as contrast enhancement agents for magnetic resonance imaging; careers for therapeutic drug, gene delivery; in magnetic separation of biological entities. Nano-sized-materials such as magnetite functionalized with albumin nanoparticles display indeed fascinating physic-chemical properties that, can be exploited to design new bio-diagnostic and therapeutic strategies. Magneted nanoparticles were used for cell labeling techniques in magnetic separation of cells. We prepared nanoparticles consisting of albumin as magnetic matrix and magnetic particles embedding, by a ultrasonic technique at temperatures of 80-95 0C. Synthesis of magnetite nanoparticles in colloidal solution by co-precipitation method from ferrous and ferric solutions were done.their physical properties and chemical stability and biocompatibility have been optimized for effective separation of cells. Characterization of magnetite with serum albumina (C_2936 H_4624 N_786 O_889 S_41) have been performed by SEM, spectrometery and difractometery (high-resolution Smartlab XDR). The morphology was invwestigate by SEM analysis. Fe3O4 nanoparticles functionalized with serum albumin were investigated for sensor applications in medicine. A microfluidic device was used to control the flow of a colloidal solution. Fluorescent detection were carried out by markers attached to the magnetic nanoparticles in order to investigate diseased cells. 18-F -fluorodeoxyglucose marker (18F-FDG) was absorbed by the magnetic nanoparticles and easily detect the damaged cells. 16:00 Transient and long term effect of SiO2 nanoparticles on invertebrate model organisms Authors : Maria Rosaria Scotto di Vettimo-1, Maria Ada Malvindi-2, Alfredo Ambrosone-1, Pier Paolo Pompa-2, Claudia Tortiglione-1, Angela Tino-1 Affiliations : 1-Istituto di Cibernetica "E.Caianiello", Consiglio Nazionale delle Ricerche, Via Campi Flegrei, 34, 80078, Pozzuoli, Italy; 2-Istituto Italiano di Tecnologia, Center for Bio-Molecular Nanotechnologies@Unile, Via Barsanti 73010 Arnesano (Lecce), Italy 27 28 29

21 sur 30 06/05/2013 09:31 Resume : The long time use of amorphous silica in cosmetics, pharmacy and food industries has constituted a strong background for the application of SiO2 NPs in biomedical research. SiO2 NPs have been extensively investigated in vitro and are considered rather biocompatible [Malvindi et al., Nanoscale, 2012], thus representing a good starting material for the development of smart drug carriers and innovative nanostructured devices. On the other hand, controversial data are available about the effect of SiO2 NPs in vivo. The freshwater polyp Hydra vulgaris has been successfully exploited by our group to assess many aspects of bio/non-bio interactions, such as tissue dynamics, and nanotoxicity. [Ambrosone et al., Biomaterials 2012]. Here we show the impact of SiO2 on Hydra. In line with the in vitro results, no toxicity effects were observed for concentrations as high as 10 nm. At higher doses, immediately after exposure, Hydra morphology, at whole animal and cellular levels was affected. Also, prolonged treatments increased such effects until lethality. The withdrawal of SiO2 restored the animal morphology and behaviour. The effects of sublethal treatments on Hydra growth-rate, regeneration, cell proliferation were quantitatively assessed together with gene expression modulation analysis. Our data provide new clues to understand the potential adverse effect played by SiO2 NPs at high doses on whole organisms, which must be taken in account when designing new devices for human purposes. 16:00 Toward polyelectrolytes nanocapsules: a novel spray synthesis of nano core of calcium carbonate (nanocaco3) Authors : Viviana Vergaro, Giuseppe Ciccarella Affiliations : Viviana Vergaro CNR NANO - Istituto di Nanoscienze Giuseppe Ciccarella CNR NANO - Istituto di Nanoscienze, Università del Salento Resume : The requested features of pharmaceutical drug delivery for intravenous administration are reasonably well met by liposomes, microcapsules, nanoparticles. Low solubility in water is an intrinsic property of many anti-cancer drugs, so there is an increasing amount of research on-going to produce functional nanometer-scale containers, and growing demand for their use in biomedical applications. In this work we have developed a novel approach to produce nanocaco3. This study represents an improvement of microcapsules synthesis, already studied in recent years in our research group. This new technique is a methodology in flow based on solution spray process through which we are able to produce nanocaco3, in a very short time, in large quantities without using surfactants or other surface modification for stabilization; it is an advantage in comparison with the other process reported in literature. The solutions of precursors are mixed and sprayed in a reaction chamber in which the high temperature allows to vaporized the water around each drop containing CaCO3. After this process controlling temperature, flow, dryness we can obtain a large amount of a very fine dry powder CaCO3 with monodispersed dimension. A combination of high resolution imaging technique such as TEM and SEM have been employed to elucidate their structure. We have performed cytotoxicity tests using different cancer cell lines. Furthermore nanocaco3 internalization has been confirmed by Confocal Microscopy. 16:00 Application of Nanoparticle Tracking Analysis (NTA) towards Characterising Nanosuspensions for Drug Delivery Authors : Pierre Peotta, Patrick Hole, Claire Hannell, Ian Wilson Affiliations : NanoSight Ltd., Amesbury, SP4 7RT, UK Resume : Nanoparticle Tracking Analysis (NTA) is a relatively new technique for the characterisation of nanomaterial suspensions. A laser beam illuminates a small scattering volume within a sample of suspended nanomaterial. The light scattered from each particle is viewed with an optical microscope and video captured with a digital camera. Each individual particle is simultaneously tracked and its Brownian motion analysed to accurately determine the particle size. This particle-by-particle approach results in a number-based concentration measurement for each size class within the distribution. The light scattering properties of nanomaterial can also be used to distinguish sub-populations within the same sample using the refractive index of nanomaterial. When used in fluorescence mode particles can be further differentiated and characterised within complex biological suspensions. Applying an electric field across the scattering volume allows nanoparticle electrophoresis (and therefore zeta potential) to be determined providing information on electrostatic repulsion and therefore colloidal stability of the sample. NTA has already been proven as a useful tool in drug delivery research for characterising liposomes, viral vaccines, synthesised nanocapsules and particle coatings for targeted drug delivery. Examples of cutting edge research using this multiparameter approach, enabling a more complete understanding of nanoscale colloids in the field of biomedicine, will be shown. 30 31

22 sur 30 06/05/2013 09:31 16:00 Preliminary approaches to prepare biocompatible and antibacterial cotton fabrics Authors : Gabriella Di Carlo*, Gabriel Maria Ingo*, Daniela Ferro*, Sergey M. Barinov#, Giuseppina Padeletti* Affiliations : *Istituto per lo Studio dei Materiali Nanostrutturati (ISMN) CNR, Via Salaria Km 29300, 00015, Monterotondo Stazione (Rome), Italy; # A.A. Baikov Institute of Metallurgy and Materials Science, Russian Academy of Sciences, Leninsky prospect 49, 119991, Moscow, Russia. Resume : The nano-hydroxyapatite (nha) has attracted much attention for application in various biomedical areas. During the last years our activity started to consider some strategies for the synthesis of hydroxyapatite as a fully biocompatible material and in a physical state suitable for biomedical applications. The actual research is mainly focused on the functionalization of cotton fabrics with hydroxyapatite and silver nanoparticles in order to realize biocompatible and antibacterial textiles, which could be used for the treatment of burns and wounds. 32 In particular, the antibacterial properties have a crucial role for the prevention of cross-infection in medical care and welfare institutions. With this aim, the present study is designed to functionalize cotton fabrics with hydroxyapatite and silver nanoparticles. The cotton fabrics have been modified with hydroxyapatite using two different types of binders: chitosan and silica sol. In addition to the deposition of hydroxyapatite, the cotton fabrics were also functionalized with silver nanoparticles by using a novel green and facile route for their preparation in contact with textile. The formation of silver nanoparticles was confirmed by UV-vis spectroscopy, due to the presence of the typical surface plasmon resonance band. The formation of nanosized silver particle onto cotton textile was also evidenced by Field Emission Scanning Electron Microscopy (FE-SEM) and their dispersion is significantly affected by the stabilizers. 16:00 Stable dispersions of Iron-based magnetic nanoparticles synthesized by laser pyrolysis Authors : C. Luculescu(1), F. Dumitrache(1), I. Morjan(1), O. Crisan(2), E. Gatin(3), S. Bengea(4) Affiliations : (1) National Institute for Lasers, Plasma and Radiation Physics, Atomistilor 409, P.O. Box MG-36, 077135 Magurele, Bucharest, Romania; (2) National Institute of Material Physics, Atomistilor 105, P.O. Box MG-7, 077125 Magurele, Bucharest, Romania; (3) Faculty of Physics, University of Bucharest, Mihail Kogalniceanu 36-46, 050107 Bucharest, Romania; (4) Faculty of Medicine, Titu Maiorescu University, Calea Vacaresti 187, 004051 Bucharest, Romania; Resume : We analyzed the dispersion behavior of hydrophobic iron based nanoparticles synthesized by laser pyrolysis in aqueous solutions. Both steric and electrostatic dispersions were achieved by ultrasonication followed by centrifugation. The dispersions were probed by DLS, Zeta potential and magnetization measurements. We report very stable electrostatic magnetic dispersions in the presence of both anionic and cationic surfactants. 16:00 Modulation of Biochemical Activity by Metal Nanoparticles: Peculiarities & Pharmaceutical Perspectives. Authors : L.S. Rieznichenko, T.G. Gruzina, A.V. Rybachuk, S.N. Dybkova, Z.R. Ulberg Affiliations : F.D. Ovcharenko Institute of Biocolloidal Chemistry; O.O. Bohomolets National Medical University Resume : Metal nanoparticles size- and concentration dependent influence on biochemical activity of living systems are under intensive studies because of its practical significance, especially for high effective diagnostic and therapy of different diseases. In order to in-vitro and in-vivo modulation of living systems biochemical activity gold, silver, iron, copper and bismuth nanoparticles with different average sizes have been synthesized by the methods of chemical reduction in water medium. Physicochemical properties of synthesized metal nanoparticles (form, size, ph etc.) have been determined. Metal nanoparticles size- and concentration dependent influence on main enzyme activities of cell plasma membrane, energy metabolism, lipid and protein peroxidation as well as state of antioxidant system has been determined for prokaryotic and eukaryotic living cells. Metal nanoparticles influence on blood chemistry indexes and distribution in organs after particles intravenous injections have been revealed for normal and pathological model animals. All obtained results indicate high pharmaceutical perspectives of some synthesized metal nanoparticles. 16:00 In vitro and in vivo biocompatibility assessment of Iron-based magnetic nanoparticles synthesized by laser pyrolysis Authors : C. Luculescu(1), S. Bengea(2), D. Savu(3), A. Acasandrei(3), M. Temelie(3), C. Mustaciosu(3) Affiliations : (1) National Institute for Lasers, Plasma and Radiation Physics, Atomistilor 33 34 35

23 sur 30 06/05/2013 09:31 409, P.O. Box MG-36, 077125 Magurele, Bucharest, Romania (2) Faculty of Medicine, Titu Maiorescu University, Calea Vacaresti 187, 004051 Bucharest, Romania (3) Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125 Bucharest-Magurele, Romania Resume : Steric dispersions of Iron-based magnetic nanoparticles synthesized by laser pyrolysis in polysaccharide aqueous solutions were used for both in vitro and in vivo biocompatibility assessment. In vitro cell proliferation assay, clonogenic assay and alkaline comet assay were performed on mouse fibroblast L929 cell and mouse melonama B16 cell lines. The cell viability is not affected for nanoparticles concentrations up to 100 µg/ml. Also, no genotoxic effects were observed for concentrations under 150 µg/ml. In vivo pyrogenicity test (the rabbit pyrogen test) proved positive for the studied magnetic nanoparticles at 1ml/kg injected volume. 16:00 Bioinspired hydroxyapatite/chitosan/l-arginine composite scaffolds for enhanced osteoconductivity Authors : Despoina Brasinika, Athena Tsetsekou, Georgios Stergiou, Ioannis Misirlis, Olga Tsigkou Affiliations : National Technical University of Athens, School of Mining and Metallurgy Engineering; University of Patras, Department of Mechanical Engineering & Aeronautics Resume : Bioinspired natural polymer scaffolds have acquired significance for bone tissue engineering applications. Considering that these scaffolds serve as a template to support and guide formation of new tissue, the material is required to be biocompatible, osteoconductive and have a porous network with high interconnectivity. However, the macroporosity inevitably affect the material s mechanical properties. The aim of this study is to synthesize composite scaffolds made of nanosized hydroxyapatite (HAp) biomolecules (chitosan and L-arginine)) by lyophilization. Without chemical cross-linking composites tend to degrade rapidly in vivo while their mechanical strength decreases. In order to add to their strength, HAp/biomolecules nanocomposites were cross-linked with glutaraldehyde (GA). Our results demonstrate improvement of the scaffolds in mechanical properties. To circumvent potential toxicity of the residual GA, the enzyme microbial transglutaminase was also evaluated as a crosslinking agent. The biocompatibility of the composites was assessed using human bone marrow derived mesenchymal stem cells (MSCs). Cell response in terms of MSC attachment (SEM) and viability/proliferation (Alamar Blue) demonstrated a non-cytotoxic effect of the new nanocomposite materials. Scanning electron microscopy, porosity measurements, X-ray diffraction and Fourier Transform Infrared Spectroscopy were used to analyze the morphology, physical and chemical properties of the composite scaffolds. 16:00 Tunable synthesis of Hybrid Copper-Chitosan Nano-antimicrobials by Femtosecond Laser-Ablation Authors : Claudio Palazzo 1, Antonio Ancona 2, Adriana Trapani 1, Teresa Sibillano 2, Francesco Mezzapesa 2, Rosaria Anna Picca 3, Matteo Cacciapaglia 3, Maria Chiara Sportelli 3, Elisabetta Bonerba 4, Giuseppina Tantillo 4, Giuseppe Trapani 1, Nicola Cioffi 3 Affiliations : 1 Pharmaco-Chemistry Department, Università degli Studi di Bari Aldo Moro, Bari, Italy; 2 IFN-CNR, Physics Department, Bari, Italy; 3 Chemistry Department, Università degli Studi di Bari Aldo Moro, Bari, Italy; 4 Department of Veterinary Medicine, Università degli Studi di Bari "Aldo Moro", Bari, Italy Resume : Nano-antimicrobials are a novel class of bioactive agents providing enhanced efficiency against biocontamination [1]. Copper nanoparticles (CuNPs) can be used under experimental conditions, such as under controlled ionic release [2], resulting in a significant inhibition of microorganism growth without being toxic for the human beings. Encapsulation of CuNPs into polymers is crucial to prevent direct NP release and possible human toxicity. Among dispersing polymers, chitosan (CS) is a well-known antimicrobial material widely exploited for its biodegradability and nontoxicity [3]. Here we report on the innovative application of the Laser Ablation Technique, operated in the femtosecond regime, to the synthesis of copper-chitosan (Cu-CS) composite nano-antimicrobials combining the bioactivity of both components [4]. Cu-CS composites were successfully obtained at different Cu/CS molar ratios in the femtosecond laser operation regime. Cu-CS hybrid nanocolloids were characterized by several techniques (UV-Vis, FTIR, DLS, TEM and XPS) to assess their surface and bulk chemical composition and morphology. Bioactivity experiments are in progress using selected microorganism strains. 1. N. Cioffi, M. Rai Eds., Nano-antimicrobials. Progress and Prospects, Springer-Verlag Publisher, 1st Edition, ISBN 978-3-642-24427-8 (2012) 2. N. Cioffi et al. Chem. Mater., 17 (2005) 5255 3. M. Kong et al., Int. J. Food Microbiol. 144 (2010) 51 4. A.E. Huh et al., J. Controlled Release 156 (2011) 128 36 37

24 sur 30 06/05/2013 09:31 16:00 Biocompatible sol-gel MgO nanoparticles for microbial growth inhibition Authors : Laura De Matteis, Valeria Grazu, Jesus M. de la Fuente, Clara Marquina, M. Ricardo Ibarra Affiliations : Laura De Matteis, Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, 50018 Zaragoza, Spain; Valeria Grazu, Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, 50018 Zaragoza, Spain ; Jesus M. de la Fuente, Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, 50018 Zaragoza, Spain, Fundacion ARAID, 50018 Zaragoza, Spain; Clara Marquina, Departamento de Física de la Materia Condensada, Universidad de Zaragoza, Facultad de Ciencias, 50009 Zaragoza, Spain, Instituto de Ciencia de Materiales de Aragon (ICMA), Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain; M. Ricardo Ibarra, Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, 50018 Zaragoza, Spain, Departamento de Física de la Materia Condensada, Universidad de Zaragoza, Facultad de Ciencias, 50009 Zaragoza, Spain Resume : Magnesium oxide is gaining attention among other ceramic materials in the field of bio-applications since its biocompatibility and its protective ability against corrosion make it an excellent material for medical purposes. So far, Mg-based materials are broadly applied as biodegradable implants and coatings on 38 alloys or polymers to improve chemical stability and biocompatibility1. As well, MgO nanoparticles (NPs) exhibit bactericidal activity that relies on the generation of ROS, due to defects or oxygen vacancies on NP surface2,3. Compared with common antibacterial NPs as silver and copper, MgO presents the advantage of biocompatibility that allows its application in a wide range of biomedical areas. Sol-gel is a very versatile and cheap method for NPs synthesis and it was employed in our work to obtain MgO NPs with a diameter of 10 nm and MgO coated magnetic NPs (15 nm)4. Bactericidal activity of MgO was tested on different bacteria; moreover, to determine the effect of the NPs on bacteria growth, the synergistic effect of NPs with antibiotics was studied in order to design an improved system for bacteria treatment. The non-cytotoxicity of the NPs in human cells was also assessed, opening broad possibilities for biomedical applications. 1 Di, D.-R.. et al., 2012, Nanomed.-Nanotechnol. Biol. Med., 8, 1233 2 Makhluf, S., et al., 2005, Adv. Funct. Mater., 15, 1708 3 Sawai, J. et al., 2000, World J. Microbiol. Biotechnol., 16, 187 4 De Matteis et al., 2012, Chem. Mat. 24, 45 16:00 Bioinspired synthesis of Hydroxyapatite nanocrystalls in the presence of Collagen and L-Arginine Authors : Despoina Brasinika, Athena Tsetsekou, Ioannis Misirlis, Olga Tsigkou Affiliations : National Technical University of Athens, School of Mining and Metallurgy Engineering; University of Patras, Department of Mechanical Engineering & Aeronautics Resume : The most promising approach for the fabrication of a real bioactive and biocompatible implant is to develop a material with similar composition, nanostructure and biological response to bone. Natural bones consist mainly of type I collagen fibrils (Col) and carbonated hydroxyapatite nanocrystalls (Hap). Research efforts are being directed towards bioinspired approaches for producing synthetic HAp nanocrystals of various morphologies employing biomolecules to modulate crystal nucleation and growth. The aim of this study is the biomimetic synthesis of HAp nanocrystals in the presence of both collagen and L-arginine, in an effort to obtain a homogeneous nanocomposite material, having a bone-like nanostructure. Collagen is the most commonly utilized protein in most species of life, while L-arginine, (Arg), encourages cell attachment, proliferation and differentiation on HAp surfaces. Scanning electron microscopy (SEM), Transmission Electron Microscopy, X-ray diffraction, Thermogravimetric Analysis and Fourier Transform Infrared Spectroscopy were used to analyze surface morphology, physical and chemical structure and crystal size of nanocomposites, with different synthesis conditions. The biocompatibility of the composites was assessed using human bone marrow derived mesenchymal stem cells (MSCs). Cell response in terms of MSC attachment (SEM) and viability/proliferation (Alamar Blue) demonstrated a non-cytotoxic effect of the new nanocomposite materials. 16:00 Detection of gold-lysozyme bio-conjugates via grating-coupled surface plasmon resonance measurement Authors : G. Bohus, A. Szalai, Á. Sipos, L. Tóth, N. Ábrahám, M. Benkő, D. Sebők, I. Dékány, M. Csete Affiliations : MTA-SZTE Supramolecular and Nanostructured Materials Research Group of the Hungarian Academy of Sciences, University of Szeged, Aradi vt 1, H 6720 Szeged, Hungary Department of Optics and Quantum Electronics, University of Szeged, H-6720 40 Szeged, Dóm tér 9, Hungary Department of Physical Chemistry and Materials Science, University of Szeged, Aradi vt 1, H 6720 Szeged, Hungary. Department of Medical Chemistry, University of Szeged, Dóm tér 8, H 6720 Szeged, Hungary Resume : Plasmonic bio-sensing chips were fabricated by generating gratings on thin polycarbonate film covered bimetal layers via two-beam interference laser 39

25 sur 30 06/05/2013 09:31 lithography method. Different Au(NP)-lysozyme bio-conjugates were prepared and the diameter of the gold nanoparticles could be altered by tuning the fraction of lysozyme in dispersions. Lysozyme is selected as an intriguing molecule having a potential to use in the field of medicine due to its antibacterial capabilities. The resulted bio-conjugates size was determined by dynamic light scattering (DLS) and small angle X-ray scattering (SAX) methods. The Au(NP)-lysozime bio-conjugates were seeded onto the surface of the grating-based bio-chips and AFM measurements were performed to determine their size and spatial distribution. Surface plasmon resonance spectroscopy was performed before and after biomolecule seeding in a modified Kretschmann-arrangement by varying the polar and azimuthal angle to optimize grating coupling conditions. The appearing secondary resonance peaks originating from rotated grating coupling were gathered to detect the bio-conjugates adherence. Finite element method calculations were performed to reproduce the absorption spectra and plasmon resonance shift originating from specific conjugates having different gold-lysozyme mass ratio. The measurements and calculation prove that the presence of gold promotes the detection of the bio-molecules. 16:00 Nanowire FET device for biomedical applications Authors : Carmen Moldovan, Adrian Dinescu, Cecilia Codreanu, Bogdan Firtat Affiliations : National Institute for R&D in Microtechnologies, Erou Iancu Nicolae, 126A, 077190 Bucharest, Romania Resume : The paper is presenting the technology of a nanowire FET device to be used in biodetection. The nanosensor we are presenting is containing a FET device realized on top of a silicon wafer substrate with a long nanowire (30microns lenght) allowing the conduction between source and drain and hosting the specific biomaterial on top of it. The FET device comprises two gates, one on the back, and one on top. The FET with double gate was realized in a unique technological process flow that will be described. The masks and the layout will be presented. The combination of UV and Electron Beam lithography allowed the rapid and efficient realization of the device. Silicon etching in TMAH provided good results in patterning a nanowire of 200nm width and 30 μm length and the BioFET nanowire manufacturing process has been achieved. The detailed technology of the device will be presented and the development of the nanowire technology as well. If a bio chemical reaction takes place or the ionic concentration of the analyte changes, the charge density on the BioFET s gate changes, too. The device selectivity is determined by the bio chemical treatment of the gate s insulator. An array of biofet devices can be used for reusable multiple-analyte sensing arrays or disposable electronic biosensors due to factors as the ever-shrinking size of FET devices, their low-power operation, their high-density fabrication methods, and their interconnectivity with micro nanoelectronic elements. 16:00 Nanostructure and multifunctional properties of butter with red beet cryopowder Authors : Rashevskaya T. A., Ivanov S. V. Affiliations : National university of food technologies, Kiev, Ukraine Resume : Nowadays whole world comes to prophylactic medicine. 70 % of all diseases bound up with nutrition. In recent years scientific direction of using bioactive compounds for prevention and treatment has developed rapidly. Nutritious vegetable substances have a lot of micronutrients with various preventive and therapeutic mechanismes, while synthetic mount has only one component. Butter is widely used product. We developed butter with red beet cryopowder (RBC). Scanning electron microscopy researches showed butter is a nanocrystall material with complex heterosystem. Addition of RBC change nanostructure of butter essentially, reduce the elements of its structure by 5-25 times in nanoscopic range. Selforganization of nanostructure was founded. Cellular nanostructure is formed with size of cellules - 60-100 nm. Mechanism of selforganization was suggested. Nanodrops of water phase and nanobumps arise in the beginning. They form the multiflat nanocrystall with nanodrops of water (8-16 nm) on edges and peaks. The fractal display is observed in nanostructure of nanocrystall. According to the results of complex researches change of butter nanostructure improves its structure and consistency, inhibits both microbiological and oxidative processes, which increase biological value and functional properties. According to the results of biomedical tests and conclusions of Ministry of Health of Ukraine butter with RBC is recommended to use for preventive and therapeutic nutrition for multifunctional biomedical application. It has bracing and immune modulating properties. Butter is recommended to use in environment with toxins and radionuclides, and also on cardiovascular diseases and some types of anemia. Aforesaid shows perspective to use RBC for butter nanostructure and functional properties management. Research shows butter is a nanoproduct. 41 42

26 sur 30 06/05/2013 09:31 16:00 Multifunctional magnetoplasmonic nanoparticles for theranostics: synthesis and ecotoxicity Authors : Marco Salmistraro, Michela Guarienti, Elena Mazzoldi, Laura E. Depero, Marco Presta, Ivano Alessandri Affiliations : M. Salmistraro; E. Mazzoldi; Laura E. Depero; I. Alessandri; INSTM and Chemistry for Technologies Lab, DIMI-University of Brescia (ITALY) M. Guarienti; M. Presta; Dipartimento di medicina molecolare e traslazionale-university of Brescia (ITALY) Resume : Nanostructures are expected to bring a decisive breakthrough in 43 biomedical technology and nanomedicine. In recent years multifunctional nanostructured materials for simultaneous imaging and therapy (theranostics) have been intensively studied. In this contribution we will present the synthesis of new core/shell nanostructures based on the combination of both magnetic and plasmonic building blocks, which are assembled in order to develop synergistic interactions. A detailed evaluation of their in vivo toxicity, based on the Zebrafish model-system, will be presented. 16:00 Magnetic Domains Interactions and Thermal Diffusivity in Magnetite Nanoparticles Authors : J. Santoyo-Salazar1, J. Hernández-Rosas2, J.L. Jiménez-Pérez2, J.A. Pescador- Rojas3, M. Vazquez4, S. Begin-Colin5 and G. Pourroy5 Affiliations : 1 Physics Department, Centro de Estudios Avanzados y de Investigación de Instituto Politécnico Nacional, CINVESTAV-IPN; 2 Unidad Profesional Interdisciplinaria en Ingenierías y Tecnología Avanzada del Instituto Politécnico Nacional, UPITA-IPN; 3 Instituto de Ciencias de Gobierno y Desarrollo Estratégico, Benemérita Universidad Autónoma de Puebla, ICGDE-BUAP; 4 Instituto de Ciencia de Materiales de Madrid, CSIC; 5 Institut de Physique et Chimie des Matériaux de Strasbourg, IPCMS Resume : The magnetic domains interactions and thermal properties of nanofluids are an especially interesting research topic because of the variety of potential applications, which range from bio-utilities to next-generation heat-transfer fluids. One of the main applications is the magnetic hyperthermia AC, which is a local cancer therapy produced by functionalized magnetite nanoparticles. The control parameters to guide and accumulate nanoparticles over the surface tumor, and generate hyperthermia depend of physical properties of magnetite, which change as function of particle size, form, stability and concentration in the nanofluid. In this work, we studied the magnetic domains interactions in magnetite, which showed uniaxial anisotropy as the particle size decreases to 10nm. Also, the thermal diffusivity of these nanofluids decreased as the size of the nanoparticles increased, and the enhancement depended on the thermal diffusivity of the solvent. The energy changes in nanofluids are associated to Neél and Brownean interactions. These results indicate that is posible to get local hyperthermia in a specific tissue by magnetic vibration until the heating is produced. 16:00 Stimuli responsive microgels for switchable biomolecular recognition Authors : Antonio Papa, Giovanni Romeo, Angela Cusano, Paolo A. Netti Affiliations : Istituto Italiano di tecnologia@crib centro di ricerca interdipartimentale sui biomateriali, universita Federico II di Napoli Resume : Sensing and recognition of bio-molecules is of extreme interest nowadays because it allows for detection of specific targets which can be the hallmarks of diseases. Colloidal particles can be used as a powerful platform to recognize molecules and to perform a fast screening of them. Indeed, in most cases the surface of colloids can be easily functionalized with agents which allow for specific recognition. In addition, colloids with a switchable recognition mechanism that can be externally triggered, would be of tremendous impact. Indeed, they would open the possibility to activate the recognition only when the particles are in specific sites. Here we show that smart particles like core-shell microgels are able to perform a reversible bio-molecular recognition mechanism. Microgels are extensively studied due to their swelling response to changes in external variables such as temperature or ph. The size change is accompanied by alterations of the particle structure. Our microgels have a N-Isopropylacrylamide (NIPAM) core coupled with a vynil acetic acid (VAA) shell. The NIPAM core introduces a temperature response of the particle size which has a steep change at a critical temperature of about T= 40 C. The caboxylic groups introduced by the VAA can be easily functionalized. We covalently bind DNA molecules to the VAA shell and show that the hybridization with complementary chains can be inverted by changing the temperature around the critical temperature of the particle. 16:00 Dendronized MnO nanoparticles for positive contrast in MRI Authors : Marc-André Fortin1, Pascale Chevallier1, Aurélie Walter2, Ilya Veksler1, Antonio Garofalo2, Delphine Felder-Flesch2, Sylvie Bégin-Colin2 Affiliations : 1-Centre de recherche du Centre hospitalier universitaire de Québec (CR-CHUQ) and Université Laval (Quebec City), 2-Institut de physico-chimie des matériaux 44 45 46

27 sur 30 06/05/2013 09:31 de Strasbourg (IPCMS) Resume : Ultra-small manganese oxide nanoparticles (MnO, 6 nm diam. core) are currently used as pre-clinical cellular and molecular positive MRI contrast agents. They are synthesized by thermal decomposition reactions, leading to small-sized hydrophobic particles. Ligand exchange procedures are needed to ensure aqueous dispersion, colloidal stability in physiological conditions and at varying ph, and the preservation of contrast properties. In this study, a new ligand based on poly(ethylene glycol)-phosphonate dendrons, of defined structure and composition, was efficiently grafted at the surface of MnO particles. The efficiency of ligand exchange on MnO particles as well as the strong involvement of phosphonate groups in the chelating process, was confirmed by XPS and FTIR. The dendronised MnO particles were stable over at least 2 weeks in water and in saline solutions, with hydrodynamic diameters of less than 100 nm. The relaxometric properties of dendronized MnO particles were measured at 1.41 T (and 37oC), and revealed r1 = 3.5 mm-1s-1 and r2/r1 close to 6. Ligand exchange with phosphonate dendrons could allow the conversion of magnetic nanoparticles into multi-modality tracers (e.g. with radioactive, fluorescent and bioactive functionalities), while limiting the sequestration of MnO particles by the reticuloendothelial system. This could be a significant step toward the synthesis of nanoparticle-based positive MRI contrast agents potentially excreted by the hepatobiliary or urinary ways. 16:00 High relaxivities and strong vascular signal enhancement for NaGdF4 nanoparticles designed for dual MR/optical imaging Authors : Marc-André Fortin1, John A. Capobianco2, Rafik Naccache2, Pascale Chevallier1, Jean Lagueux1, Yves Gossuin3, Sophie Laurent4, Luce Vander Elst4, Cornelia Chilian5 Affiliations : 1- Centre de recherche du Centre hospitalier universitaire de Québec (CR-CHUQ) and Department of Engineering Materials Université Laval (Quebec City) 2- Department of Chemistry and Biochemistry and Centre for NanoScience Research Concordia University (Montreal) 3- Service de physique expérimentale et biologique Université de Mons 4- Service de chimie générale organique et biomédicale Université de Mons 5- Laboratoire Slowpoke, Ecole Polytechnique de Montréal Resume : Upconverting NaY(Gd)F4:Tm3+,Yb3+ nanoparticles are capable of undergoing NIR-to-NIR (near-infrared) upconversion and are efficiently detected by NIR imaging techniques. As they contain Gd3+, they can also be used as positive MRI contrast agents. In this study, NaY(Gd)F4:Tm3+,Yb3+ nanoparticles of two sizes (inf. to 5 nm and ~25 nm core diam.) were synthesized by thermal decomposition, capped with citrate, dispersed in water and characterised by XRD, TEM, XPS, as well as fluorescence studies in the visible and NIR regions. The colloids were measured by dynamic light scattering (DLS), and the proton relaxation times (T1, T2), measured by NMR relaxometry. Ultra-small NaGdF4:Tm3+,Yb3+ (inf. to 5 nm diam.) provided high relaxivities (r1 = 3.37 mm-1s-1 at 1.41 T and 37 oc) and the lowest relaxometric ratios (r2/r1 = 1.18) reported for NaGdF4 nanoparticle suspensions. NMRD profiling revealed strong relaxivity peaks in the range of 20-300 MHz for both small (~25 nm) and ultra-small nanoparticles. Ultra-small nanoparticles showed a strong positive contrast enhancement effect at magnetic field strengths higher than 1 T. Mice that were injected i.v. with ultra-small NaGdF4 particles, showed strong vascular for at least 90 minutes. Nanoparticle biodistribution studies were performed at 48h and 8 days. This study confirms that ultra-small NaGdF4 nanoparticles have promising luminescent, relaxometic and blood-retention properties for dual MRI/optical imaging. 16:00 Bio-compatible small-molecule coatings for iron oxide magnetic nanoparticles prepared via thermal decomposition Authors : G. Salas, M. P. Morales Affiliations : G. Salas: IMDEA Nanociencia and Instituto de Ciencia de Materiales de Madrid; M. P. Morales: Instituto de Ciencia de Materiales de Madrid Resume : The most common procedure for the synthesis of iron oxide magnetic nanoparticles (IONPs) is the co-precipitation method and, thus, the development of new coatings for preparing IONPs for biomedical applications is far more explored for those obtained by co-precipitation than for any other method. On the other hand, the high-temperature decomposition of an iron precursor in an organic solvent is an arguably better way to produce highly monodisperse IONPs, with better size control and magnetic properties than in the co-precipitation method. However, IONPs obtained by thermal decomposition are hydrophobic which means that, for biomedicine, surface modification is needed to yield bio-compatible nanomaterials. This issue is not always trivial and is usually accomplished with different polymers. Small molecules have been explored in less extent, although they can provide IONPs with smaller hydrodynamic sizes (Z-average sizes = 50-100 nm), which can be advantageous, depending on the specific application. In this 47 48

28 sur 30 06/05/2013 09:31 work we study the surface modification of hydrophobic IONPs with small molecules covalently bound to nanoparticle surface, as dimercaptosuccinic acid and phosphonates, to yield bio-compatible IONPs with suitable properties for biomedical applications. These IONPs have charged surfaces in a wide range of ph, which may serve to functionalize them with active molecules or drugs. 16:00 T1 contrast agent for magnetic resonance imaging using MgFe2O4 nanoparticles Authors : V.V. Pankov, D.A. Kotsikau, E.G. Petrova Affiliations : Belarusian State University Resume : In comparison with conventional gadolinium helates, nanoparticle-based contrast agents for MRI offer enhanced cellular internalization. Iron oxide nanoparticles were the first and are the most commonly used magnetic nanoparticle-based contrast agents. Recently, however, there has been a growing interest in low temperature sintered MgZn ferrite because of its better properties at high frequencies and ferrites are more biocompatible than well-known Fe3O4 or γfe2o3 particles. A samples with Mg0.5 Zn0.5Fe2O4 chemical composition was prepared by modified spray pyrolysis of inorganic metal precursors. Mg2+, Zn2+, Fe3+ nitrates were taken in stoichiometric proportion, and NaCl (50 wt. % of nitrates) was added as an inert component. Finally, NaCl additive was thoroughly removed from the powders after annealing. Modified spray pyrolysis technique helps avoid aggregation of particles during the ferrite phase formation. T1 and T2 relaxation times were measured and the correlation of magnetic properties of MgZn ferrite with their MR relaxivities in water was determined. The MgZn ferrite consists of grains with a predominate size of 5-20nm. Saturation magnetization values were measured to be 32, 60 and 81 emu/g for 300, 15 and 7 K, respectively. 16:00 Development of T2 contrast agent for magnetic resonance imaging using MgFe2O4 nanoparticles. Authors : V.V. Pankov, D.A. Kotsikau, E.G. Petrova Affiliations : Belarusian State University Resume : In comparison with conventional gadolinium helates, nanoparticle-based contrast agents for MRI offer enhanced cellular internalization. Iron oxide nanoparticles were the first and are the most commonly used magnetic nanoparticle-based contrast agents. Recently, however, there has been a growing interest in low temperature sintered MgZn ferrite because of its better properties at high frequencies and ferrites are more biocompatible than well-known Fe3O4 or γfe2o3 particles. A samples with Mg0.5 Zn0.5Fe2O4 chemical composition was prepared by modified spray pyrolysis of inorganic metal precursors. Mg2+, Zn2+, Fe3+ nitrates were taken in stoichiometric proportion, and NaCl (50 wt. % of nitrates) was added as an inert component. Finally, NaCl additive was thoroughly removed from the powders after annealing. Modified spray pyrolysis technique helps avoid aggregation of particles during the ferrite phase formation. T1 and T2 relaxation times were measured and the correlation of magnetic properties of MgZn ferrite with their MR relaxivities in water was determined. The MgZn ferrite consists of grains with a predominate size of 5-20nm. Saturation magnetization values were measured to be 32, 60 and 81 emu/g for 300, 15 and 7 K, respectively. 16:00 Novel Dextran-Based Nanogels: a Flexible platform for constructing Drug Delivery Systems and Biomarker Agents Authors : Shuyan Zhou1, Hongjing Dou1,*, Zhaofeng Zhang2, Yuqing Jin2, Zunli Shen2, Kang Sun1 Affiliations : 1 The State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. E-mail: hjdou@sjtu.edu.cn 2 Department of Plastic and Reconstructive, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China. Resume : Nanogels have long been regarded as promising drug delivery system (DDS) for their biocompatibility, stability, and especially stimuli responsiveness. Doxorubicin (DOX) is a widely used chemotherapeutic agent in cancer treatments, but its application is strongly restricted due to its short biological half-life and nonspecific biodistribution. It is well known that tumor tissues possess lower ph value than normal tissues, as well as the over-expression of folic acid receptors [1]. On this basis, here we designed and successfully prepared a smart drug delivery system from dextran-based nanogels. We synthesized monodisperse poly(methyl acrylate) modified dextran nanogels (DM NGs) with the hydrodynamic diameter of about 100 nm by a one-pot approach developed by our group [2], and further conjugated DOX through ph-labile hydrazone bond by reacting DM NGs with excessive amount of hydrazinium hydroxide and then DOX (DMDOX NGs) [3]. Folic acid (FA) was also conjugated to the nanogel through amide condensation to offer active targeting of nanogels (DMDOX FNGs) to solid tumor. All reaction products 49 50 51

29 sur 30 06/05/2013 09:31 were confirmed by 1H-NMR. Both Dex-PMA-DOX NGs with or without FA showed a ph dependent release of DOX with 60% at ph 5.0 and only 20% at ph 7.4 after 60 h, which indicated the successful linkage of DOX through hydrazone bond. MTT assays with HeLa cells showed little toxicity of the DM NGs, while DMDOX FNGs were very effective in delivering DOX into the nucleus of HeLa cells by fluorescence microscope observation after co-incubating DMDOX FNGs with HeLa cells for 24 h. Owing to their FA active targeting, passive targeting of EPR (enhanced permeation and retention) effect, and ph responsive drug release, DMDOX FNGs are very promising as one kind of new DDS for anti-cancer therapeutics. In addition, adipose-derived stem cells (ADSCs) possess extensive proliferative capacity and potential to differentiate into multiple cell lineages, thus has been widely used in tissue engineering and regenerative medicine. In order to understand its migration and differentiation after being transplanted into human body, various ways has been tried out to track and label ADSCs. The dextran based nanogels, as a flexible carrier, can be further conjugated with a fluorescence dye 5-aminofluorescein (5-AF) to build fluorescently label ADSCs. Our study indicated that NGFs are very promising in ADSCs imaging. Acknowledgements: This work was supported by the National Natural Science Foundation of China (No. 20904032, 21174082). References: [1] F. Danhier, O. Feron, V. Préat, To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery, J. Control. Release 148(2010) 135-146. [2] M.H. Tang, H.J. Dou, K. Sun, One-step synthesis of dextran-based stable nanoparticles assisted by self-assembly, Polymer 47(2006) 728-734. [3] L. Zhou, R. Cheng, H.Q. Tao, S.B. Ma, W.W. Guo, F.H. Meng, H.Y. Liu, Z. Liu, Z.Y. Zhong, Endosomal ph-activatable poly(ethylene oxide)-graft-doxorubicin prodrugs: synthesis, drug release, and biodistribution in tumor-bearing mice, Biomacromolecules 12(2011) 1460-1467. 16:00 NMR Spectra of Octacalcium Phosphate with Two Kinds of Dicarboxylic Acid Co-incorporated in Interlayers Authors : Hirotaka Fujimori, Yoshiaki Miyamoto, Taishi Yokoi, Chikara Ohtsuki Affiliations : Dept. of Applied Chem., Yamaguchi Univ., Japan; Dept. of Crystalline Mater. Sci., Grad. Sch. of Eng., Nagoya Univ. Japan Resume : We have successfully obtained 31P and 13C NMR spectra of octacalcium phosphate carboxylate (OCPC) with suberic and succinic acids co-incorporated in the interlayers. According to 31P NMR spectra, total peak intensity of phosphorus located in the hydrated layer of OCPC is smaller than that of undoped OCP. This indicates HPO42- in the hydrated layer is replaced by incorporated dicarboxylate ions. The 13C NMR spectra indicate there are two molecular orientations of carboxyl groups existing in OCPC. Moreover, each amount of co-doped suberic and succinic acids in OCPC was estimated. 16:00 Synthesis of magnetic nanoparticles of Fe2O3 @ SiO2 in microreactors Authors : Paulina Lloret, Gloria Longinotti, Gabriel Ybarra, Carlos Moina Affiliations : Instituto Nacional de Tecnologia Industrial Laboratorio de Nanomateriales Resume : This paper presents the one-step synthesis of SiO2 magnetic nanoparticles prepared in continuous flow microreactors. SiO2 particles are readily functionalizable with organic groups which serve as linkers to attach biomolecules as used in biosensors. Magnetic cores can be preconcentrated and can be moved with the aid of an external magnet which allows measurements with a higher detection level. To obtain nanoparticles is necessary to control the stages of nucleation and growth in order to obtain monodisperse sizes and reproducibility. In the synthesis of nanoparticles by batch system there are some disadvantages that make the process difficult and unrepeatable to obtain monodispersed particles. This is basically due to the inhomogeneity of reagents and temperature in the reaction medium, leading to the synthesis of particles varies between different lots. Continuous flow microreactors has the advantage of operating in laminar regimes where the synthesis of particles is less affected by the effect of diffusion of reactants and where the inside temperature control is achieved quickly and efficiently, avoiding gradients temperature. The synthesis of nanoparticles was carried out by coating iron oxide nanoparticles of 15 nm in diameter with SiO2 layer by Sol-Gel method. Microreactors of 4 ml capacity were used at different residence times and temperatures. Adjusting the residence times, the need of grafting the iron NP is avoided. Particles with diameters in the range150-400 nm were obtained. The particles presented a low size dispersion and showed good magnetic properties. Functionalizated nanoparticles were used as protein carriers for the detection of foot-mouth desease by electrochemical biosensor. Magnetic SiO2 nanoparticles have demonstrated to be a suitable material for life science. 52 53

30 sur 30 06/05/2013 09:31 Back European Materials Research Society 23 Rue du Loess - BP 20-67037 Strasbourg Cedex 02 - France - Phone:+33-(0)3 88 10 63 72 - Fax:+33-(0)3 88 10 62 93 - emrs@emrsstrasbourg.com

1 sur 6 06/05/2013 09:31 PROGRAM VIEW : 2013 Spring MY PROGRAM : 2013 Spring Symposium : U Design of multifunctional nano-objects for biomedical applications 27 May 2013 28 May 2013 29 May 2013 30 May 2013 31 May 2013 hide a start at Subject Num. INteraction of nanoparticles with cells : C. Menager - Nguyen TK Thanh 08:30 Mixed Ligand Nanoparticles and Cell Membranes Authors : Francesco Stellacci Affiliations : Institute of Materials, Ecole Polytechnique Fédérale de Lausanne Resume : In recent years there has been an increasing attention to the use of nanomaterials for medicine. These innovative materials are used to generate new medical devices (e.g. electrodes for neuronal activity), for in vitro / in vivo imaging/drug-delivery, or for regenerative purposes. Understanding and controlling the interaction between these materials and the complexity of all biological elements is one of the key challenges to achieve safe and efficient use. Many factors play a role, ranging from the nanomaterials size, shape, and chemical composition all the way to their colloidal stability and chemical reactivity. In this talk we will highlight the role of ligand shell composition and structure in the interaction with cell membranes as well as with lipid bilayers. In particular a novel method to measure this interaction with lipid bilayers will be presented. 09:00 Designed Fabrication of Multifunctional Nanobiomaterials for Active Modulation of Cells and Tissues Authors : Jaeyun Kim Affiliations : Laboratory for Nanobiomaterials and Regenerative Medicine, Sungkyunkwan University, Suwon, Korea Resume : Materials-based therapeutic strategy has paved the way to overcome various limitations in current conventional and clinical approach to treat diseases. Here we present our recent research achievements using various nanobiomaterials for active modulation of cell and tissues for the treatment of cancer, ischemia, Type I diabetes. Each material system was designed on demand according to its potential use in therapeutic applications. Multifunctional nanostructured materials were designed for simultaneous cancer diagnosis and therapy. Magnetic gold nanoshells consisted of gold nanoshells embedding magnetite nanoparticles, polymer nanoparticles possessing magnetite and doxorubicin, and uniform-sized core/shell nanoparticles composed of magnetite core and dye-dpoed mesoporous silica shell were demonstrated in their uses in simultaneous MRI/fluorescent imaging and photothermia/drug delivery in cancer. To increase efficacy of proangiogenic factor delivery to treat ischemic disease, we evaluated nanoparticles for their targeting to ischemic tissue via EPR effect due to hypoxia and demonstrated nanoparticles could deliver VEGF to ischemic tissue to enhance blood perfusion. In islet transplantation in Type I diabetic patients, protecting transplanted cells from immunorejection as well as long-term noninvasive imaging are required. We designed alginate capsulein-capsule where contrast agents and human islets are located in core and secondary alginate shell, respectively. Preventing direct exposure of cells to contrast agent while providing a larger confinement space for transplanted cells allowed not only trimodal imaging with MRI, CT, and ultrasound, but also high insulin secretion for a long period. 09:15 Effect of metal oxide nanoparticles on human tumoral cells. Induction of activation pathways and changes in gene expression Authors : Rosana Simon-Vazquez, Tamara Lozano-Fernandez, Andrea Hernandez- Fernandez, Africa Gonzalez-Fernandez Affiliations : Immunology, Biomedical Research Center (CINBIO), University of Vigo, Campus Lagoas Marcosende, 36310, Vigo, Pontevedra, Spain Resume : The potential use of metal oxide nanoparticles (NPs) in biomedicine is 13 1 13 2 13 3

2 sur 6 06/05/2013 09:31 being tested for diverse applications such as contrast agents for imaging. To characterize the possible toxicological effects on different cell types, the activation of MAPKs and NFkB induced by four different metal oxide NPs (ZnO, TiO2, CeO2 and Al2O3) have been studied in two different tumoral cell lines, NCI-H460 (lung) and Jurkat (T cell). Additionally, the lymphocyte cell line was tested in the presence or absence of phytohemaglutinin (PHA). The changes in gene expression on Jurkat cell line have been further characterized for the activation of other signal transduction pathways by qpcr. The results indicate that Jurkat cells, after incubation with the different metal oxide NPs, were more susceptible to the activation of the route of MAPKs when compare to the NCI-H460 cells. Only ZnO NPs were able to induce the activation of SAP/JNK in both cell lines, in accordance with the cytotoxic effect observed with these NPs. The pattern of activation showed differences depending on the previous activation induced by PHA compared to cells without stimulation, and depending on the type of NP used. While ZnO and Al2O3 NPs were able to activate the NFkB pathway in both cell lines, TiO2 NPs only activated this pathway on Jurkat cells. Activation of genes involved in cell cycle, metabolism, apoptosis and other cellular events were also detected by qpcr. 09:30 Localization and radiosensitizing effect of Gd nanoparticles in cancer cells Authors : Lenka Štefančíková1, Erika Porcel2, Pierre Eustache2, Stanislav Kozubek1, Martin Falk1 and Sandrine Lacombe2 Affiliations : 1 Laboratory of Chromatin Function, Damage and Repair, Institute of Biophysics, ASCR, Brno, Czech Republic 2 Institute of Molecular Sciences (ISMO), University Paris Sud, Orsay, France Resume : Nanoparticles (NPs) dedicated to biomedical applications are in fast development, especially in the perspective of cancer treatment. In particular, NPs composed of high-z atoms are proposed as potential nanodrugs to improve tumor targeting and increase the therapeutic index of radiotherapy. The mechanism of tumor sensitization by NPs is probably attributed to the auto-amplification of electronic cascades within the NPs, which causes highly lethal nanoscopic damage in their vicinity (Porcel et al., 2010). Experiments performed at molecular scale confirm that these effects are due to fast electronic processes. It was demonstrated that the combination of lanthanide NPs and irradiation by X-rays (Le Duc et al., 2011), gamma rays as well as with incident carbon ions (Lacombe and co-workers, paper in preparation) efficiently decreases the survival of tumor cells. In this work, we describe the effect of NPs, composed of GdO2 core and polysiloxane shell (GdNPs) (Roux et al., 2010), on the survival of the radioresistant U87 cancer cell line irradiated by protons. To understand the mechanism of radiosensitization of tumors by NPs the crucial information is their localization in the cells and the way of their internalization. Using complementary microscopic techniques we clearly showed that: 1) the GdNPs stay in the cytoplasm of the cells and do not enter into the nuclei (confocal microscopy using fluorescently labeled NPs and deep ultraviolet microscopy enabling to observe the intrinsic fluorescence of NPs) 2) the GdNPs are internalized in cells via endocytosis (transmission electron microscopy showing the first steps of endocytosis as well as vesicles containing NPs within the cytoplasm, confocal microscopy with concentrated fluorescently labeled NPs) 3) the GdNPs colocalize with lysosomes but not with mitochondria in later time post incubation (confocal microscopy using fluorescently labeled probes visualizing lysosomes and mitochondria, respectively). Radiation induced cell death is considered to be caused predominantly by double strand breaks (DSBs) in nuclear DNA. Thus, we wanted to know whether the mechanism of radio-sensitization by GdNPs includes also effects on DNA damage and repair. In this context, we have studied the induction, persistence, and disappearance of radiation-induced γ-h2ax and 53BP1 repair foci after incubation of cells with GdNPs and their irradiation by gamma rays. The results clearly show that the synergic effect of radiotherapy and GdNPs is not related to the induction of DSBs in nuclear DNA. These results are in good agreement with our previous observations showing that NPs are localized in the cytoplasm and do not penetrate into the nucleus. In conclusion, GdNPs are potent radiosensitizers upon different types of irradiation. They penetrate into the cytoplasm by endocytosis but probably do not enter the nucleus. The presence of NPs within the cytoplasm affects neither the induction nor the repair of DSBs. The mechanism of radiosenzitization as a cytoplasmic event requires further elucidation. The work was supported by the following projects: GAČR P302/12/G157, COST LD12039 (MŠMT), ECOST MP1002 Nano IBCT, ECOST- STSM-MP1002-030612-017920, GAČR P302/10/1022, OPVK CZ.1.07/2.3.00/30.0030 Porcel E, Liehn S, Remita H, Usami N, Kobayashi K, Furusawa Y, Le Sech C, Lacombe S. Platinum nanoparticles: a promising material for future cancer therapy? Nanotechnology 2010; 21, p. 85103 Roux S, Tillement O, Billotey C, Coll JL, Duc GL, Marquette CA, Perriat P. Multifunctional nanoparticles: from the detection of biomolecules to the therapy. Int. J Nanotech 2010; 7: 781-801. Le Duc G, Miladi I, Alric C, Mowat P, Bräuer-Krisch E, Bouchet A, Khalil E, Billotey C, Janier 13 4

3 sur 6 06/05/2013 09:31 M, Lux F, Epicier T, Perriat P, Roux S, Tillement O. Toward an image-guided microbeam radiation therapy using gadolinium-based nanoparticles. ACS Nano 2011; 5: 9566-9574. 09:45 Development of metalloproteinase-sensitive nanoparticles for tumor-activated doxorubicin release Authors : Marco Biondi, Daniela Guarnieri, Hui Yu, Valentina Belli, Paolo Antonio Netti Affiliations : Marco Biondi: Dipartimento di Chimica Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, Napoli, Italy. Centro di Ricerca Interdipartimentale sui Biomateriali (CRIB), Università di Napoli Federico II, Piazzale Tecchio 80, Napoli, Italy. Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Daniela Guarnieri: Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Hui Yu: Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Valentina Belli: Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy; Paolo Antonio Netti: Centro di Ricerca Interdipartimentale sui Biomateriali (CRIB), Università di Napoli Federico II, Piazzale Tecchio 80, Napoli, Italy. Center for Advanced Biomaterials for health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti, Napoli, Italy. Dipartimento di Ingegneria dei Materiali e della Produzione, Università di Napoli Federico II, Piazzale Tecchio 80, Napoli, Italy. Resume : Among endopeptidases, matrix metalloproteinase-2 (MMP2) is minimally expressed in normal tissues while being present at high concentrations in active tumor sites. MMP2 is involved in matrix breakdown, and is therefore thus crucial to tumor angiogenesis and invasion. Thus, the incorporation of MMP2-cleavable domains in nanoparticles (NPs) is regarded as a novel control strategy for the localized release of chemotherapeutics to tumors. In this context, the aim of this study was to synthesize a tumor-activated prodrug (TAP) made up of poly(ethylene glycol) (PEG) and doxorubicin (Dox) conjugated to MMP2-cleavable peptides. The TAP was tethered to model polystyrene (PS) NPs (200 nm diameter). Dox release kinetics were quantified in presence and absence of MMP2, and NP cytotoxicity towards human fibrosarcoma (HT1080), human dermal fibroblast (HDF) and human vein endothelial cells (HUVEC) cells was assessed. Results indicated that Dox release is increasingly favoured with increasing MMP2 concentrations. Cytotoxicity was studied for 7 days, and cell death was triggered in presence of MMP2. In all cases, the cytotoxicity due to NP-conjugated Dox was lower compared to the free drug. More specifically, NPs not preliminarily treated with MMP2 showed minimal cytotoxicity in all cases, and this effect was particularly evident against tumor cells (HT1080). In conclusion, TAP-conjugated NPs are attractive as safe tumor-specific delivery systems. 13 5 10:00 Coffee break Nanoparticles for imaging 2 : R. Bentes de Azevedo - P. Morales 10:30 Bioorthogonal Functionalisation of Nanoparticles for pulmonary and cardiovascular molecular imaging Authors : B.Salinas, H. Groult, J. Ruiz-Cabello, F. Herranz Affiliations : Advanced Imaging Unit. Dpt of Epidemiology, Atherothrombosis and Imaging. Spanish Cardiovascular Research Centre (CNIC) and Spanish Pulmonary Research Centre (CIBERES) Resume : The bioorthogonal functionalisation of different types of nanoparticles for molecular imaging has been carried out. We have used two bioorthogonal approaches to obtain nanoparticles biologically active providing signal in several imaging techniques, like Magnetic Resonance Imaging (positive and negative contrast) and Fluorescence Imaging. These techniques are, first, the olefin metathesis that we have applied, for the first time to the functionalisation of iron oxide nanoparticles. And, the second, the specific molecular recognition between the oleic acid coated nanoparticles and albumin. These new techniques have been applied to two types of nanomaterials, iron oxide nanoparticles and up-converting nanophosphors. We have obtained iron oxide nanoparticles with extremely long circulating time in blood, after intravenous injection in mice, of 24 hours and dual imaging signal. We have also developed up-converting nanoparticles, providing signal in MRI and Fluorescence, that selectively accumulate in the lung after i.v. injection showing that this accumulation can be detected in vivo by MRI and Fluorescence. F. Herranz; J. Pellico; J. Ruiz-Cabello. SPIE Newsroom. 2012. DOI: 10.1117/2.1201209.004473 B. Salinas; J. Ruiz-Cabello; M. P. Morales; F. Herranz. 14 1

4 sur 6 06/05/2013 09:31 Bioinspired, Biomimetic and Nanobiomaterials. 2012, 1-3, 166-172. F. Herranz; C. B. Schmidt-Weber; M. H. Shamji; A. Narkus; J. Ruiz-Cabello; R. Vilar. Contrast Media & Molecular Imaging. 2012, 7-4, 435 439. 11:00 In Vivo Near Infrared FRET Imaging of Nanoparticle Accumulation and Dissociation Kinetics in Tumor Bearing Mice Authors : Yiming Zhao, Inge van Rooy, Sjoerd Hak, Francois Fay, Jun Tang, Aurelian Radu, Zahi. A. Fayad, Celso de Mello Donegá, Andries Meijerink and Willem Mulder Affiliations : Condensed Matter and Interfaces, Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 5, 3584 CC Utrecht, The Netherlands; Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA; Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA; MI Lab and Department of Circulation and Medical Imaging, The Norwegian University of Science and Technology, Trondheim, Norway Resume : In the last decade self-assembled lipidic nanoparticles have been increasingly explored as intravenously injectable agents for biomedical purposes. They can serve as drug delivery vehicles and/or molecular imaging probes. Particularly, lipid-coated inorganic nanocrystals are of great interest as such nanoparticles exhibit unprecedented possibilities with respect to their multifunctionality, potential for derivatization and biocompatibility.[1] Although many lipidic nanoparticles have been developed and applied in vivo for cancer diagnosis and therapy, most studies failed to consider two essential questions: Do these self-assembled particles retain their original composition, and how do they disassemble at and clear from the targeted site? Therefore, an improved understanding of the in vivo dynamics of the lipidic nanoparticles and subsequent trafficking of the different nanoparticle components would allow an improved tailoring of nanoparticle design to application. To this aim, we here introduce a PEG-lipid stabilized nanoparticle that is composed of a near infrared (NIR) quantum dot (QD) core and a NIR dye-lipid corona label (QD-Cy7-PEG).[2] This nanoparticle allowed us to investigate the dynamics of nanoparticle accumulation and dissociation in a tumor mouse model. The large spectra separation between the QD and Cy7-lipid enable us to trace them simultaneously by using an NIR fluorescence imaging system in vivo. Moreover, Förster resonance energy transfer (FRET) between the QD core and the Cy7-lipid allowed us to sensitively monitor nanoparticle dissociation. Upon intravenous administration of the nanoparticles, the disassociation process was observed through a decrease of FRET signal in the tumors in vivo. Ex vivo organ imaging revealed the QD nanocrystal core and the lipid coating to follow different clearance pathways. In vivo imaging experiments with mice that received peritumoral injections of QD-Cy7-PEG revealed its trafficking to sentinel lymph nodes. Through fast protein liquid chromatography analyses of blood plasma, we found the nanoparticle s lipid coating vividly exchanged with plasma proteins as well as lipoproteins. In conclusion, our study allowed in vivo imaging of the accumulation, dissociation and trafficking of lipidcoated nanocrystals. Our technology helps optimizing and tailoring design criteria when using lipid-coated nanocrystals for biomedical purposes in general, and our results warrant caution in the interpretation of imaging data when using them as diagnostic agents specifically. 1. T. Skajaa, Y. Zhao et al. Nano Lett. 2010, 10,5131 2. Y. Zhao, I. van Rooy et al. unpublished 11:15 Synthesis and study of superparamagnetic iron oxide nanoparticles: the effect of the particle size and an iron oxidation state on magnetic and NMR relaxivity properties Authors : Vladimir L. Kolesnichenko, Galina Z. Goloverda, Pavel Kucheryavy, Jibao He, Vijay T. John, Pawan Maharjan, and Leonard Spinu Affiliations : Xavier University, Chemistry Department University of New Orleans, Physics Department Tulane University, Department of Chemical and Biomolecular Engineering New Orleans, Louisiana, USA Resume : Application of the superparamagnetic iron oxide nanoparticles in biology and medicine finds its rapidly developing emphasis on the contrast agents for MRI. Due to their high magnetic moment, superparamagnetic nanoparticles enhance the proton relaxation predominantly via outer-sphere mechanism and therefore act as negative (T2) contrast agents. Positive contrast imaging, which is utilized due to the interaction of protons with high-spin transition metal ions (usually GdIII), is frequently preferred in a diagnostic practice, however the existing gadoliniumcontaining T1 contrast agents raise substantial toxicity issues. In addition, a relatively high mobility of such agents shortens their presence in the vascular system. These drawbacks stimulate the researcher s effort on the development of T1 contrast agents based on ultrasmall superparamagnetic iron oxide particles. The best currently known blood pool MRI agents are based on iron oxides and 14 2 14 3

5 sur 6 06/05/2013 09:31 considered non-toxic. Reducing the particle size below 5 nm can lower their magnetic moment, and therefore the outer-sphere relaxivity r2. At the same time, a larger surface-to-volume ratio of these small particles can cause a greater involvement of the iron atoms in the spin-lattice relaxation process, which relies on direct water coordination and exchange at the metal sites. Consequently, the particle size reduction can be a way to obtaining a better T1 contrast agent. The crystal structure and magnetic properties of the ferrimagnetic iron oxides magnetite and maghemite are known to have a subtle difference. A study on how the particle size, magnetic susceptibility and an iron oxidation state affect the relaxivity properties of the nanoparticles will be reported. 11:30 Ultra-stable and high quality PEGylated Fe3O4 nanoparticle aqueous suspensions: tracer for magnetic particle imaging Authors : A. Lak, F. Ludwig, J. M. Scholtyssek, T. Wawrzik, and M. Schilling Affiliations : Institut für Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Hans-Sommer- Str. 66, 38106 Braunschweig. Resume : Iron oxide nanoparticles reveal promising physiochemical properties, making them a promising candidate for a variety of nanoparticle-based diagnostics and therapeutics, such as medical imaging (magnetic resonance imaging (MRI) and magnetic particle imaging (MPI)), targeted drug delivery and hyperthermia. MPI is a recently emerged modality with a great potential for real time imaging of magnetic nanoparticle distribution with high sensitivity and spatial resolution. Although performing a reliable MPI experiment depends significantly upon the dynamic and static magnetic properties of the tracer being used, merely a few studies have been dedicated to optimization of iron oxide nanoparticles specifically for MPI. In this study, high quality monodisperse magnetite nanoparticles with a mean core size of 20 nm have been transferred into water via exchanging their ligands with hydroxyl terminated PEG-nitrodopamine. The particles labeled with functional PEG moieties have a great biomedical potential owing to their non-toxicity and versatility for further functionalization. The success of the ligand exchange reaction has been confirmed by IR spectroscopy and TGA analysis. The PEGylated nanoparticles with a median hydrodynamic size of 90 nm have shown an excellent long term stability over one month. Their MPI performance was investigated by Magnetic Particle Spectroscopy (MPS) known as zero dimensional MPI. To do this, a MPS setup operating at an excitation frequency of 10.05 khz with an amplitude of 20 mt has been employed. The odd harmonics spectrum of the PEGylated iron oxide nanoparticles reveals a large number of odd harmonics, indicating their potential for being a capable MPI tracer. The results of real MPI experiments will be presented and discussed. Acknowlegment The financial support by the Braunschweig International Graduate School of Metrology (B-IGSM) for PhD thesis (A.L.) is acknowleged. 11:45 CO-ENCAPSULATION OF CuInS2@ZnS QDs AND Fe3O4 NPs FOR MULTIMODAL IMAGING BIOMEDICAL APPLICATIONS Authors : I. X.Cantarelli1, E. Fantechi2, F. Boschi3, E. Mosconi4, P. Marzola4, G. Conti1, M. Pedroni1, F. Piccinelli1, C. Sangregorio5, A. Speghini1 Affiliations : 1Dipartimento di Biotecnologie and INSTM, Unità di Verona,Università di Verona, Strada le Grazie 15, 37134 Verona, Italia; 2INSTM and Dipartimento di Chimica U. Schiff, Università di Firenze, via della Lastruccia 3, 50019 Sesto Fiorentino, Italia; 3Dipartimento di Scienze Neurologiche, Neuropsicologiche, Morfologiche e Motorie, Università di Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italia; 4Dipartimento di Informatica, Università di Verona, Strada le Grazie 15, 37134 Verona, Italia; 5CNR-ISTM and INSTM, via C. Golgi 19, 20133 Milano, Italia. Resume : I-III-VI semiconductor quantum dots (QDs), including CuInS2@ZnS (CIS@ZnS), are of great interest for in vitro and in vivo biomedical imaging applications due to their tunable and strong emission in spectral regions close to the biological window (650-900 nm), making them interesting for deep tissue fluorescence imaging [1]. In order to obtain simultaneously optical and MRI (magnetic resonance imaging) active nanoparticles (NPs), in the present investigation, CIS@ZnS QDs were embedded with Fe3O4 NPs, well known MRI contrast agent, in larger nanocomposites. To this purpose, hydrophobic CIS@ZnS QDs were synthesized in an organic solvent adapting a procedure reported in the literature [2]. Oleate capped Fe3O4 NPs were prepared by thermal decomposition of iron acetyacetonate in a high boiling solvent [3]. The hydrophobic QDs and Fe3O4 NPs were thereafter simultaneously transferred in water solution using a co-encapsulation strategy based on an amphiphilic molecule. The obtained nanocomposites are stable for at least two weeks. Preliminary studies on the optical and relaxivity properties will be presented together with cytotoxicity studies. [1] L. Li, T.J. Daou, I. Texier, T.T.K. Chi, N.Q. Liem, P. Reiss, Chem. Mater. 2009, 21, 2422-2429. [2] L. Li, A. Pandey, D.J. Werder, B.P. Khanal, J.M. Pietryga, V.I. 14 4 14 5

6 sur 6 06/05/2013 09:31 Klimov, J. Am. Chem. Soc. 2011, 133, 1176-1179. [3] C.A. Crouse, A.R. Barron, J. Mater. Chem. 2008, 18, 4146-4153 Back European Materials Research Society 23 Rue du Loess - BP 20-67037 Strasbourg Cedex 02 - France - Phone:+33-(0)3 88 10 63 72 - Fax:+33-(0)3 88 10 62 93 - emrs@emrsstrasbourg.com