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181025 presentation by daniela wilson (smb living lab meeting 25 10-18)

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Presentation Self-assembled Polymeric Nanoparticles by Daniela Wilson SMB Meeting dd 25-10-2018

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181025 presentation by daniela wilson (smb living lab meeting 25 10-18)

  1. 1. Autonomous Self-Assembled Polymeric Nanoparticles with Controlled Movement and Directionality for Biomedical Applications Prof. dr. Daniela A. Wilson d.wilson@science.ru.nl Radboud University Nijmegen Institute for Molecules and Materials Nijmegen - The Netherlands
  2. 2. Nanomedicine Theme: Research lines (1)  Cellular & Extracellular Nano-organizations (2) Precision Diagnostics & Therapies Innovative diagnostic concepts Novel therapeutic approaches Fundamental cell functions & Mimetic structures - protein structure and folding -dynamic protein-protein interactions - structure-function relationship -extracellular matrix mimics
  3. 3. Motion Regulated transport Regulating the shape and function of supramolecular assemblies - Emergent Systems Selective transport Adaptive Nanosystems Angew. Chem. Int. Ed, 2015, 54, 11662 Soft Matter, 2014, 10, 1295. J. Mater. Chem B. 2014, 2, 2395. Nanoscale 2013, 5, 1315. Nature Chem. 2012, 4, 268-274. J. Am. Chem. Soc. 2016, in press Nature Commun. 2014, 5, 5010 Chem. Commun. 2014, 50, 5394. J. Am. Chem. Soc. 2012, 134, 9894 Nanomotors Nanoreactors Chem. Rev. 2016 Collective behavior Systems colonies Biomimetic Non-equilibrium Systems Dynamic & Interactive Systems at interface between chemistry- physics and bioscience Nature Commun. 2016 Nanolett 2018
  4. 4. Challenge: Precise Directional Control Nanocarrier design
  5. 5. Pictures from Google images 1.  Design of building blocks with smart encoded functionality STRUCTURE 3. Soft Supramolecular Assemblies SHAPE, SIZE, FUNCTIONALITY 2. Catalyst design CATALYTIC ACTIVITY Active, Autonomous Particles with Adaptive Behaviour Towards Intelligent Life-like systems 4. Biomimmetic Design of Functions MOTILITY, COMUNICATION, ADAPTIVE BEHAVIOUR
  6. 6. Tuning the Size High Tg •  Addition rate/Concentration •  Sonication •  Temperature (T) •  Microfluidics Supramolecular Approach
  7. 7. Tuning the Shape High Tg •  Osmotic pressure •  Temperature (T) •  Additives: surfactants, PEG, polymers Jacs 2010, Nature Commun 2014, 5, 5010; Nature Commun 2016, Supramolecular Approach
  8. 8. Nature Commun 2014, 5, 5010; Chem Commun 2014, 50, 5100 Control of the Shape •  different shapes via out-of-equilibrium self-assembly: nm to micron Probing morphological changes IN SITU 2T EX-SITU (cryo)-TEM, SEM
  9. 9. Self-propelled polymer particles APRIL 2012 VOL 4 NO 4 www.nature.com/naturechemistry Nature Chem. 2012 (News & Views: Nature Chem. 2012), JACS 2013, Nanoscale 2013 Autonomous Particles with Regulatory Functions
  10. 10. Nanomotor Assembly: Supramolecular Approach PtNP-driven Nanomotors H2O2 2H2O2 O2 + 2H2O PtNP PtNP: - platinum nanoparticles Nature Chem. 2012, 4, 268-274 9;
  11. 11. Proof of Entrapment Cryo-TEM & Electron Tomography Z = 180 Bart de Nijs Wilson, D. A.* et. al. Nanoscale 2013, 5, 1315.
  12. 12. Movement Analysis NTA – Nanoparticle Tracking Analysis Nanosight LM10 LM10 Nature Chem. 2012, 4, 268-274 9; x,y( ) 4 2 = Dt Stokes Einstein KB = Boltzmann Constant η = viscosity T = Temperature
  13. 13. Nature Chem. 2012, 4, 268-274 Highlighted in News & Views: Nature Chem. 2012, 4, 247-248 ; Nanoscale 2013, 5, 1315. 350 nm V= 23 μm/s V= 66 body lengths/s V= 800 km/h PtNP driven Nanomotors 371 cm No FUEL 20 μL FUEL 15 μL FUEL Tracking the trajectories <r2> = 4DΔt + (vΔt)2 Movement analysis
  14. 14. Drug loaded PtNP driven Nanomotors 371 cm Angew. Int. Ed. 2015, 54 (40) 11662 Fei
  15. 15. Activated neutrophils: Motors sense gradients of H2O2 (0 - 2 mM H2O2) Chemotaxis towards cells 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 Challenge1: Control of directionality?
  16. 16. Sensing small gradients of H2O2 Chemotaxis towards model cells Fei Directionality control: a. b. Angew. Int. Ed. 2015, 54 (40) 11662
  17. 17. Guidance with Magnetic Field f Steering and change in direction Magnetotaxis through collagen mesh Adv. Mater. 2016, DOI: 10.1002/adma.201604996 Guidance towards Hella cells
  18. 18. •  selective access •  light responsive •  redox, T, or pH responsive •  release of content Switching on/off nanomotor UV valve Temperature valve Advantages Challenge 2:Control of the Movement?
  19. 19. Switching on/off nanomotor Ying Temperature Responsive Valve Nature Chem. 2017, DOI: 10.1038/nchem.2674
  20. 20. Functioning of the Valve Nanosight NS500 Control of the Movement Switching on/off nanomotor
  21. 21. 0 10 20 30 40 50 30 32 34 36 38 40 T/ ºC Velocityμm/s OPEN CLOSED Three ON-OFF Cycles Motion at different T Control of the Movement Switching on/off nanomotor
  22. 22. before encapsulation after encapsulation Challenge 3: Multiple (Bio) Fuels Enzyme Powered Nanomotor
  23. 23. Enzymes 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; ACS Central Sc. 2017, DOI 10.1021/acscentsci.6b00254 •  Enzyme Cascade •  Enzyme network - Regulation possible (Adaptive System) Catalytic System:
  24. 24. Autonomous Movement in Blood Serum •  Movement at physiological concentrations of glucose! •  Operation at ultra low concentrations of glucose 0.05-10 mM!
  25. 25. Autonomous Movement 2.5 mM Glucose
  26. 26. Applications of Supramolecular Nanomotors Self-guided particles Ultimate Goal •  Actively seek and precisely locate diseased tissue •  Truly active delivery system! Current Approach: Passive Ligands Drug •  Biocompatible •  Sense gradients •  Fast diffusion •  Move directionally New Approach: Active Requirements
  27. 27. Active Delivery in Biosystems Faster uptake: Enhanced EPR: Janus Polymersome Nanomotor Adv. Funct. Mater. 2018,1706117 Angew. Chem. Int. Ed. 2017, 56 (26), 7620 Chem Commun 2017, 53, 1088 ACS Nano 2017, DOI:10.1021/acsnano.6b08079
  28. 28. Biodegradable Systems Microgel asymmetric particles Biodegradable tubes
  29. 29. Active & Autonomous Polymeric Particles – New Therapies Controlled Size and Shape, Drug loading, Controlled Motion Active, Autonomous and Adaptive Chemotaxis Increased Cellular Uptake Enhanced EPR 100 nm Wilson DA et al., Nature Chem 2017, DOI: 10.1038/nchem.2674 ACS Nano 2016,10 (2), 2652–2660; Angew. Int. Ed. 2015, 54 (40) 11662 •  Signal amplification by substrate recycling •  Movement in plasma •  Movement at physiological concentrations 6 enzyme “The Fantastic Voyage” – nanomotors for targeted drug delivery and diagnostics - actively seeking and precisely locating disease tissues by sensing disease signalling molecules.
  30. 30. Acknowledgments PhD’s Fei Peng Yinfeng Tu Loai Abdelmohsen Roger Rikken Jiamian Wang Shauni Keller Jelle Toebes Jiawei Sun Wei Li Sjoerd Rikema • 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 Collaborators Yongjun Men Alaa Adawy Gajanan Pawar Marlies Nijemeisland Motilah Isamar Ortiz-Rivera Post-docs MSc Alain André Josje Heuvelmans Sema Gizem Özel Wei Li Ashish Adhikari Rian Jeucken

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