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.

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. 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”
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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. 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. 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. 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
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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. Tuning the Shape
High Tg
• Osmotic pressure
• Temperature (T)
• Additives: surfactants, PEG,
polymers
Nature Commun 2014, 5, 5010; Nature Commun 2016,
Supramolecular Approach

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. Self-propelled supramolecular polymeric nanomotor
Pioneering Study – ERC Starting Grant 2012
Nature Chem. 2012 (News & Views: Nature Chem. 2012), JACS 2013, Nanoscale 2013

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

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

16. Guidance with Magnetic Field
f
steering
Magnetotaxis through collagen mesh
Adv. Mater. 2016,
DOI: 10.1002/adma.201604996

17. New Strategy: Solvent Addition Method
Biocatalyst: Enzyme Encapsulation
Gajanan, Loai
ACS Nano, 2016, 10 (2), 2652–2660

18. Enzyme Powered Nanomotor
before encapsulation after encapsulation
Loai
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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:
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20. Autonomous Movement2.5 mM Glucose

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. Acknowledgments
Thank you for your attention!!!!
FUNDING
ERC-StG, STOMA MOTOR
Inovational Incentive Scheme, VIDI
Athena Award
Aspasia Grant
EU, EuroMagNet