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Ecole Polytechnique Fédérale Lausanne, EPFL Powder Technology Laboratory

Nanoparticles for Diagnostic and Therapeutic Applications The Potential of SuperParamagnetic Iron Oxide Nanoparticles (SPION). Heinrich Hofmann. Ecole Polytechnique Fédérale Lausanne, EPFL Powder Technology Laboratory. Content. Introduction Some remarks regarding physical,

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Ecole Polytechnique Fédérale Lausanne, EPFL Powder Technology Laboratory

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  1. Nanoparticles for Diagnostic and Therapeutic Applications The Potential of SuperParamagnetic Iron Oxide Nanoparticles(SPION) Heinrich Hofmann Ecole Polytechnique Fédérale Lausanne, EPFL Powder Technology Laboratory

  2. Content • Introduction • Some remarks regarding physical, • colloidal and physiological properties • Diagnosis: • Specific targeting, protein “fishing”, • molecular imaging • Therapy: • Gene and drug delivery, Hyperthermia • Conclusions

  3. + + Superparamagnetic Iron Oxide Nanoparticle QuantumDots

  4. SPION: some physical properties Transport Relaxation Brown Néel rh>>rm

  5. attraction b repulsion magn. field lines • Magnetic interaction between particles

  6. Zeta potential () potential near to the outer Helmoltz Plan particle surface Colloidal Stability • Electrostatic interactions • Steric interactions • Polyelectrolyts (Polyethylenimide PEI, etc) • Magnetically induced interactions

  7. Changes in polymer and protein adsorption and /or conformation Dawson Conformation changes of the PVA at the particles surface (swelling, hyrogel)

  8. Agglomeration in physiological liquids D = DMEM; R = RMPI P: PVA, A: amino-PVA Agglomeration rate in nm/h) Fink-Petri, Hofmann

  9. Inlet tube 0.2% Agarose gel SPIONs suspension Magnet Coating stability

  10. Superparamagnetic Iron Oxide Particles Research Protein identification nanoESI-MS/MS Spec. adsorption at cell surfaces organelles, ECM proteins Particle library SDS-PAGE Mag separation and concentration Diagnosis Quantitative detection Magnetic, ELISA Particle derivatized with specific antibodies

  11. Multifunctional Core-shell Nanoparticles Highly complex compounds: • Core: magnetic and/or fluorescent materials • Shell I: inorganic materials (SiO2.. • Shell II: functionalizable layer (COOH, SH, NH2..) • Therapeutic and/or imaging payload • „Stabilizer“ • Targeting moieties APS-SPIONs (~25-35 nm; + 33 mV) Magnetic immobilization of SPION PEG-APS-SPIONs 1 hr recirculation (~70 nm & -20 mV) FL-protein-PEG-APS-SPIONs cysteine-protein-FL-PEG-APS-SPIONs (~80 nm & -13 mV) APS: aminopropyltriethoxysilane

  12. Protein and organelle targeting Hsp 90 Hsp 70 1-9 3-oxoacyl-thiolase presequence Extra cellular matrix SPION with ALEXA and NTP QPSPSPTGC Hsp 75 dye cRGD Hsp 60 Annexin1+2 cytoplasm mitochondria Integrin Malate dehydrogenase ATP synthase Tubulin Glycolysis enzymes (4) Transketolase + Rest 48 out of 58 proteins could be related to: Up-take mechanism, transport to mitochondria, mitochondria membrane, including energy related processes. Evidence view of the protein interaction network in STRING

  13. Molecular Imaging X. Montet University of Geneva, Particles from EPFL-LTP

  14. Magnetic Implant Hyperthermia CT scan Implant Injectable Nanoparticle/ Monomer solution Implant External magnetic field 143 kHz, 12 mT 3-D CT scan

  15. Gene and Drug delivery Magnet

  16. Gene transfection with oscillating magnetic fields 293T cells 293T cells 293T cells 293T cells synoviocytes Nucleic Acids Research, 2006, Vol. 34, No. 5 e40

  17. Conclusions • The magnetic properties of SPION opens interesting opportunities for novel diagnostic and therapeutic methods: • Specific adsorption (molecular imaging, protein detection, early detection of diseases • Hyperthermia • enhanced transfection, drug delivery • Stem cell tracking • Protein-Particle interaction is one of the most important factor

  18. Acknowledgement Alke Petri-Fink, Jatuporn Salaklang, Benedikt Steitz, Andrija Finka, Conlin P. O'Neil, Marc Moniatte, André J. van der Vlies, Todd D. Giorgio,, Jeffrey A. Hubbell, Xavier Montet SNF, CTI, EU FP5, EU-FP7, ESM, ANTIA Therapeutics Literature Jatuporn Salaklang, et al. Superparamagnetic Nanoparticles as a Powerful Systems Biology Characterization Tool in the Physiological Context; Angewandte Chemie International Edition, Volume 47, Issue 41, 2008,  7857-7860 Petri-Fink A ,et al., Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): Colloidal stability, cytotoxicity, and cellular uptake studies EUROPEAN JOURNAL OF PHARMACEUTICS AND IOPHARMACEUTICS    Vol 68, 129-137, 2008   Steitz B, et al Fixed bed reactor for solid phase surface derivatization of superparamagnetic nanoparticles Bioconjugate Chemistry, Vol 18  1684-1690, 2007

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