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

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. 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. 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. Challenge: Precise Directional Control
Nanocarrier design

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. Tuning the Size
High Tg
• Addition rate/Concentration
• Sonication
• Temperature (T)
• Microfluidics
Supramolecular Approach

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. 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. 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. Nanomotor Assembly: Supramolecular Approach
PtNP-driven Nanomotors
H2O2
2H2O2 O2 + 2H2O
PtNP
PtNP: - platinum nanoparticles
Nature Chem. 2012, 4, 268-274 9;

11. Proof of Entrapment
Cryo-TEM & Electron Tomography
Z = 180
Bart de Nijs
Wilson, D. A.* et. al. Nanoscale 2013, 5, 1315.

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. 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. Drug loaded PtNP driven Nanomotors
371 cm
Angew. Int. Ed. 2015, 54 (40) 11662
Fei

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. Sensing small gradients of H2O2
Chemotaxis towards model cells
Fei
Directionality control:
a. b.
Angew. Int. Ed. 2015, 54 (40) 11662

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. • 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. Switching on/off nanomotor
Ying
Temperature Responsive Valve
Nature Chem. 2017, DOI: 10.1038/nchem.2674

20. Functioning of the Valve
Nanosight NS500
Control of the Movement
Switching on/off nanomotor

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. before encapsulation after encapsulation
Challenge 3: Multiple (Bio) Fuels
Enzyme Powered Nanomotor

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. Autonomous Movement in Blood Serum
• Movement at physiological concentrations of glucose!
• Operation at ultra low concentrations of glucose 0.05-10 mM!

25. Autonomous Movement
2.5 mM Glucose

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. 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. Biodegradable Systems
Microgel asymmetric particles Biodegradable tubes

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. 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