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1 - SPRING 13 U: Design of multifunctional nano-obj sur 2 06/05/ :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 Please see the link for more details and submission: /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

2 - SPRING 13 U: Design of multifunctional nano-obj sur 2 06/05/ :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: Etienne Duguet Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB) 87 ave du Dr Albert Schweitzer F Pessac Cedex France Phone: Puerto Morales Instituto de Ciencia de Materiales de Madrid Consejo Superior de investigaciones Cientificas Sor Juana Ines de la Cruz , Madrid Spain Phone: Claire Billotey Laboratoire de Physico-Chimie des Matériaux Luminescents UMR 5620 CNRS-UCBL Université Claude Bernard Lyon 1 10 rue Ada Byron Villeurbanne cedex France Phone: Sylvie Begin Institute of Physic and Chemistry of Materials of Strasbourg (IPCMS) 23, rue du Loess, BP Strasbourg cedex France Phone: European Materials Research Society 23 Rue du Loess - BP Strasbourg Cedex 02 - France - Phone:+33-(0) Fax:+33-(0)

3 1 sur 25 06/05/ :29 PROGRAM VIEW : 2013 Spring MY PROGRAM : 2013 Spring Symposium : U Design of multifunctional nano-objects for biomedical applications 27 May May May May 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, 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 Illkirch, France; Laboratoire de Biotechnologie et signalisation cellulaire, CNRS (UMR 7242), Ecole supérieure de biotechnologie Strasbourg, 300 Boulevard Sébastien Brant 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

4 2 sur 25 06/05/ :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, [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, [3] D. Mertz, H. Wu, J. S. Wong, J. Cui, P. Tan, R. Alles, F. Caruso, Journal of Materials Chemistry 2012, 22, :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 , Korea; 2Department of biomedical laboratory science, College of Health Sciences, Yonsei University, Wonju,

5 3 sur 25 06/05/ :29 Gangwondo , 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, 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

6 4 sur 25 06/05/ :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: Salas G, et al. Controlled synthesis of uniform magnetite nanocrystals with high-quality properties for biomedical applications. J Mater Chem 2012; 22: :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 Villeurbanne cédex 2 CREATIS UMR CNRS 5220 U1044 Inserm, F 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 :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

7 5 sur 25 06/05/ :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, 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

8 6 sur 25 06/05/ :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, Genova, Italy Teresa Pellegrino;National Nanotechnology Laboratory of CNR-NANO, Via per Arnesano, 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

9 7 sur 25 06/05/ :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

10 8 sur 25 06/05/ :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

11 9 sur 25 06/05/ :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, Kyiv, Ukraine; Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64, Kyiv, Ukraine; Ilmenau University of Technology, Institute of Chemistry and Biotechnology, Weimarer Str. 25, 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 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

12 10 sur 25 06/05/ :29 National University of Kyiv, Volodymyrska Str., 64, Kyiv, Ukraine; Technical University of Ilmenau, Institute of Chemistry and Biotechnology, Weimarer Str., 25, 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

13 11 sur 25 06/05/ :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, Magurele, Romania; 4 INFIM Institute, PO Box MG. 7, Magurele Bucharest, Cod , Romania; 5 St. Pantelimon Hospital, Sos Pantelimon Nr , 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, :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 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

14 12 sur 25 06/05/ :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, Strasbourg cedex 2, France 2 LPCML-UCBL UMR 5620, Service de Médecine Nucléaire Pavillon B, 5 place d Arsonval, Lyon cedex 03, France 3 UMR 990 INSERM/Université d'auvergne, 58 rue Montalembert, 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, W. Tuong, L.S. Cheng, A.W. Armstrong, Dermatologic Clinics, 2012, 30, D.A Tomalia, A.M. Taylor, W.A. Goddard, Angew. Chem., Int. Ed., 1990, 102, , F.M. Veronese, G. Pasut, DDT, 2005, 10, :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

15 13 sur 25 06/05/ :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 , 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, 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 14 sur 25 06/05/ :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, 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, 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 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

17 15 sur 25 06/05/ :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, 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, 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

18 16 sur 25 06/05/ :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 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

19 17 sur 25 06/05/ :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 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

20 18 sur 25 06/05/ :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, Volos, Greece; (2) Department of Physics, Aristotle University of Thessaloniki, Thessaloniki, Greece; (3) Analytical Chemistry Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, 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 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 structures. Galvanic replacement reaction is the difficulty in synthesizing while successful formation of must overcome lattice mismatch. This oral focuses on our recent results in the study of 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

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