Nanotechnology in a historical perspective

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1 Nanoparticles for medical applications Maria Kempe Biomedical Polymer Technology Biomedical Center, Lund University Phone: Nanotechnology in a historical perspective Nanoparticles: Size and shape Design of multifunctional nanoparticles Examples of synthetic and natural nanoparticles FDA-approved nanoparticles Nanoparticles for medical applications: Diabetes Cardiovascular disease Cancer Infection/inflammation Solid-phase synthesis & screenings

2 Richard Feynman ( ) Lecture in 1959: There is plenty of room at the bottom Why cannot we write the entire 24 volumes of the Encyclopedia Britannica on the head of a pin? A friend of mine (Albert R. Hibbs) suggests a very interesting possibility for relatively small machines. He says that, although it is a very wild idea, it would be interesting in surgery if you could swallow the surgeon. You put the mechanical surgeon inside the blood vessel and it goes into the heart and ``looks'' around. (Of course the information has to be fed out.) It finds out which valve is the faulty one and takes a little knife and slices it out. Other small machines might be permanently incorporated in the body to assist some inadequately-functioning organ. Ancient nanotechnology The Lycurgus cup, ca. 300 AD (Rome) nm Ag-Au-alloy nanoparticles Reflected light Transmitted light Luster pottery (metal nanoparticles) Mesopotamia 900 AD Nanostructured pigments Egyptian blue Maya blue Falu rödfärg (hematit, Fe2O3) Majolica 1550 AD

3 Ancient nanotechnology Egyptian hair dyeing formula PbS nanoparticles form in situ from PbO and Ca(OH)2 in presence of Cys t=0 t=6h Longitudinal section of 3-day-treated hair Walter et al. Nano Lett. 2006, 6, Size matters Nanos (νᾶνος) = dwarf t = 72 h

4 Nanos (νᾶνος) = dwarf Size matters 30 nm

5 Nanomedicine the application of nanotechnology to medicine Chemistry Physics Nanomedicine Life Sciences Engineering Multifunctional nanoparticles Imaging x-ray/ct MRI fluorescense/nir PET/SPECT US Drug delivery small molecules proteins RNA Cell internalization cell-penetrating peptides Targeting antibodies ligands magnetic targeting Biocompatibility coating self-peptides

6 Examples of nanoparticles Liposomes and micelles Dendrimers Silica nanoparticles Iron oxide nanoparticles Quantum dots Gold nanoparticles Natural nanoparticles (ferritin, HDL, LDL, virus, vault NPs, etc) Examples of FDA-approved nanoparticles Abelcet: amphotericin B (1995) Abraxane : paclitaxel (taxol) bound to albumin (2005) Doxil (Caelyx) pegylated liposome with doxorubicin (1995)

7 Shape matters Dahlström & Kempe, unpublished Choi & Alivisatos Annu. Rev. Phys. Chem : Champion et al. PNAS 2007, 104, Shape matters Breast cancer-targeting antibody (trastuzumab) immobilized to PS NPs Nanospheres Nanorods Nanodiscs Highest internalization in breast cancer cell lines with rods Highest cell growth inhibition with rods Higher cell growth inhibition with immobilized antibody than with soluble antibody Barua et al PNAS 2013, 110,

8 Nanoparticles for! Kempe et al. Biomaterials 2010, 31, Gu et al. ACS Nano 2013, 7, Kempe et al. Expert Rev. Med. Devices 2011, 8, Nanoparticles for Handle Kempe, et al., submitted for publication Norén & Kempe. Int. J. Pept. Res. Ther. 2009, 15,

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