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170411 nanomedicine new strategies in targeted delivery (daniela wilson), innoboot 2017

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Publication of presentation by dr. Daniela Wilson, theme leader Nanomedicine at Radboud University Science Faculty on New strategies in targeted delivery. Innoboot 2017, Nijmegen, The Netherlands on April 11, 2017.

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170411 nanomedicine new strategies in targeted delivery (daniela wilson), innoboot 2017

  1. 1. Theme: NANOMEDICINE New strategies in targeted delivery Daniela A. Wilson d.wilson@science.ru.nl Radboud University Nijmegen Institute for Molecules and Materials Nijmegen - The Netherlands 4e Innovation Bootcamp
  2. 2. Theme: NANOMEDICINE “From molecules to supramolecular assemblies ” Nanomedicine – medical application of nanotechnology Chemistry Biology design synthesis characterization Nanomedicinemolecules proteins structure function nanostructured devices Tissue repairImaging & diagnostics Targeted delivery Cell-like structures Challenges: “understand and elucidate structure and function” “ design biomimetic systems and processes” 4e Innovation Bootcamp
  3. 3. Imaging & diagnostics Targeted delivery Chemical biology Dynamic Biomimetic Systems molecular probes eg. tumor spatial temporal control transport mechanisms single cell analysis BIG data data analysis prodrug strategies-de/re-activation drugs particles & nanobodies futuristic nanodrug carriers tissue specificity intracelular delivery theranostics elucidate biological processes molecular switches, chemical epigenetics, glycosylation/glycobiology bio-orthoganol chemistry in living cell Self-organization in cell-like structures domain/raft formation, intracellular organisation, extracellular environments, artificial cell platforms Theme: NANOMEDICINE “From molecules to supramolecular assemblies” 4e Innovation Bootcamp
  4. 4. 4e Innovation Bootcamp Initiatives EFRO 2017 – LAB NANOMEDICINENANOMEDICINE ALLIANCE develop radical new therapies “testing environment” Few partners to validate applications Enabling technology and production
  5. 5. Motion Regulated transport Regulating the shape and function of supramolecular assemblies - Emergent Systems Selective transport Adaptive Nanosystems Nanomotors Nanoreactors Collective behavior Systems colonies Biomimetic Non-equilibrium Systems Smart Functional Systems at interface between chemistry- physics and bioscience
  6. 6. Active Delivery in Biosystems Self-guided nanomotors Ultimate Goal • Actively seek and precisely locate tumors (prostate cancers) • Truly active delivery system! Current Approach: Passive Ligands Drug • Biocompatible • Sense gradients • Fast diffusion • Move directionally New Approach: Active Requirements 4e Innovation Bootcamp
  7. 7. Bacteria Sperm Movement FuelStructure Pictures from Google images  Direction  Speed  Flagellum/Cilia  Soft  ATP Nature: Inspiration for Nanomotors Biological Micro/Nanomotors 4e Innovation Bootcamp
  8. 8. Tuning the Shape High Tg • Osmotic pressure • Temperature (T) • Additives: surfactants, PEG, polymers Nature Commun 2014, 5, 5010; Nature Commun 2016, Supramolecular Approach
  9. 9. Nature Commun 2014, 5, 5010; Chem Commun 2014 Control of the Shape • different shapes via out-of-equilibrium self-assembly Probing morphological changes IN SITU 2T EX-SITU (cryo)-TEM, SEM
  10. 10. Self-propelled supramolecular polymeric nanomotor Pioneering Study – ERC Starting Grant 2012 Nature Chem. 2012 (News & Views: Nature Chem. 2012), JACS 2013, Nanoscale 2013
  11. 11. Nanodrug carriers of tomorrow! H2O2 2H2O2 O2 + 2H2O PtNP PtNP: - platinum nanoparticles & enzyme Nature Chem. 2012, 4, 268-274 9; Biomimetic Locomotive Nanocarriers 4e Innovation Bootcamp
  12. 12. Chemotaxis towards cells: Motors sense gradients of H2O2 (0 - 2 mM H2O2) Control of Motion and Directionality Motors are followed in space (1,2,3) and time Cells in Petri dish Immobilized cells Directional movement Angew. Int. Ed. 2015, 54 (40) 11662 4e Innovation Bootcamp
  13. 13. Sensing small gradients of H2O2 Chemotaxis towards model cells Fei Directionality control: a. b. Angew. Int. Ed. 2015, 54 (40) 11662
  14. 14. • selective access • light responsive • redox, T, or pH responsive • release of content Switching on/off nanomotor UV valve Temperature valve Advantages Control of the Movement
  15. 15. Functioning of the Valve Nanosight NS500 Control of the Movement Switching on/off nanomotor
  16. 16. Guidance with Magnetic Field f steering Magnetotaxis through collagen mesh Adv. Mater. 2016, DOI: 10.1002/adma.201604996
  17. 17. New Strategy: Solvent Addition Method Biocatalyst: Enzyme Encapsulation Gajanan, Loai ACS Nano, 2016, 10 (2), 2652–2660
  18. 18. Enzyme Powered Nanomotor before encapsulation after encapsulation Loai 4e Innovation Bootcamp
  19. 19. Enzyme Powered Nanomotor V= 61 μm/s V= 176 body lengths/s 1, 2, 3, …6 enzymes FUEL: H2O2, Glucose, Lactate ACS Nano 2016,10 (2), 2652–2660 • Enzyme Cascade • Enzyme network - Regulation possible (Adaptive System) Catalytic System: 4e Innovation Bootcamp
  20. 20. Autonomous Movement2.5 mM Glucose
  21. 21. Acknowledgments PhD’s Loai Abdelmohsen Fei Peng Yinfeng Tu Roger Rikken Jiamian Wang Shauni Keller Jelle Toebes •R.J.M. Nolte, J.C.M. van Hest, W. Huck- Institute for Molecules and Materials, Radboud University Nijmegen, The Netherlands •B. de Nijs, B., A. van Blaaderen, Utrecht University , The Netherlands •P.G. van Rhee, P.C.M. Christianen, J. C. Maan - High Field Magnet Laboratory, Radboud University Nijmegen, The Netherlands •Virgil Percec, University of Pennsylvania , USA • Mike Klein, Temple University, USA My Group Collaborators Yongjun Men Alaa Adawy Gajanan Pawar Marlies Nijemeisland Post-docs MSc Alain André Josje Heuvelmans Sema Gizem Özel Wei Li Ashish Adhikari Rian Jeucken
  22. 22. Acknowledgments Thank you for your attention!!!! FUNDING ERC-StG, STOMA MOTOR Inovational Incentive Scheme, VIDI Athena Award Aspasia Grant EU, EuroMagNet

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