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Autonomous	Self-Assembled	Polymeric	
Nanoparticles	with	Controlled	Movement	and	
Directionality	for	Biomedical	Application...
Nanomedicine	Theme:	Research	lines	
(1)  Cellular	&	Extracellular	Nano-organizations	
	
	
	
	
(2)	Precision	Diagnostics	&	...
Motion
Regulated transport
Regulating	the	shape	and	function	of	
supramolecular	assemblies		
-	Emergent	Systems	
Selective...
Challenge:	Precise	Directional	Control	
Nanocarrier	design
Pictures	from	Google	images	
1.  Design	of	building	
blocks	with	smart	
encoded	functionality	
STRUCTURE	
	
3.	Soft	Supram...
Tuning	the	Size	
High	Tg	
	
•  Addition	rate/Concentration	
•  Sonication	
•  Temperature	(T)	
•  Microfluidics	
Supramole...
Tuning	the	Shape	
High	Tg	
	
•  Osmotic	pressure	
•  Temperature	(T)	
•  Additives:	surfactants,	PEG,	
polymers		
Jacs	201...
Nature	Commun	2014,	5,	5010;	Chem	Commun	2014,	50,	5100		
	
Control	of	the	Shape	
•  	different	shapes	via	out-of-equilibr...
Self-propelled polymer particles
APRIL 2012 VOL 4 NO 4
www.nature.com/naturechemistry
Nature	Chem.	2012	(News	&	Views:	Nat...
Nanomotor Assembly: Supramolecular Approach	
PtNP-driven	Nanomotors		
H2O2	
2H2O2	 O2	+	2H2O	
PtNP	
PtNP:	-	platinum	nanop...
Proof of Entrapment
Cryo-TEM & Electron Tomography	
Z	=	180	
Bart	de	Nijs	
Wilson,	D.	A.*	et.	al.	Nanoscale	2013,	5,	1315.
Movement Analysis
NTA – Nanoparticle Tracking Analysis
Nanosight LM10
LM10
Nature	Chem.	2012,	4,	268-274	9;		
x,y( )
4
2
=...
Nature	Chem.	2012,	4,	268-274	
Highlighted	in	News	&	Views:	Nature	Chem.	2012,	4,	247-248	;	Nanoscale	2013,	5,	1315.	
350 ...
Drug	loaded	PtNP	driven	Nanomotors		
371 cm
Angew.	Int.	Ed.	2015,	54	(40)	11662	
Fei
Activated	neutrophils:	
Motors	sense	gradients	of	H2O2	(0	-	2	mM	H2O2)	
Chemotaxis	towards	cells	
Motors	are	followed	in	s...
Sensing	small	gradients	of	H2O2	
Chemotaxis	towards	model	cells	
Fei	
Directionality	control:	
a.	 b.	
Angew.	Int.	Ed.	201...
Guidance	with	Magnetic	Field	
	
f	
Steering	and	change	in	direction	
Magnetotaxis	through	collagen	mesh	
Adv.	Mater.	2016,...
• 		selective	access	
• 		light	responsive	
• 	redox,	T,	or	pH	responsive		
• 	release	of	content	
Switching	on/off	nanomo...
Switching	on/off	nanomotor	
Ying	
Temperature	Responsive	Valve	
	
Nature	Chem.	2017,	DOI:	10.1038/nchem.2674
Functioning	of	the	Valve	
	
Nanosight	NS500	
Control	of	the	Movement	
	
Switching	on/off	nanomotor
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	...
before	encapsulation																																											after	encapsulation		
Challenge	3:	Multiple	(Bio)	Fuels	
En...
Enzymes	Powered	Nanomotor	
V=	61	μm/s	
V=	176	body	lengths/s	
1,		
2,		
3,		
…6	enzymes	
FUEL:	H2O2,	Glucose,	Lactate	
ACS...
Autonomous	Movement	in	Blood	Serum	
•  Movement	at	physiological	concentrations	of	glucose!	
•  Operation	at	ultra	low	con...
Autonomous	Movement	
	
2.5	mM	Glucose
Applications	of	Supramolecular	
Nanomotors	
Self-guided	particles	
		
Ultimate	Goal	
• 		Actively	seek	and	precisely	locat...
Active	Delivery	in	Biosystems	
		
Faster	uptake:		 Enhanced	EPR:	
Janus	Polymersome	Nanomotor	
Adv.	Funct.	Mater.	2018,170...
Biodegradable	Systems	
	Microgel	asymmetric	particles	 Biodegradable	tubes
Active	&	Autonomous	Polymeric	Particles	
–	New	Therapies	
Controlled	Size	and	Shape,	Drug	loading,	Controlled	Motion	
Acti...
Acknowledgments	
											PhD’s 		
Fei	Peng	
Yinfeng	Tu	
Loai	Abdelmohsen	
Roger	Rikken	
Jiamian	Wang	
Shauni	Keller	
Je...
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181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 1 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 2 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 3 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 4 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 5 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 6 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 7 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 8 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 9 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 10 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 11 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 12 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 13 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 14 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 15 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 16 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 17 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 18 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 19 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 20 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 21 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 22 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 23 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 24 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 25 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 26 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 27 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 28 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 29 181025 presentation by daniela wilson (smb living lab meeting 25 10-18) Slide 30
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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

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

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