Imperial College London
Alternate

Professor Molly Stevens

Faculty of Engineering, Department of Materials

Professor of Biomedical Materials and Regenerative Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6804m.stevens

 
 
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Location

 

208Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Massi:2020:10.1039/D0TB01546F,
author = {Massi, L and Najer, A and Chapman, R and Spicer, C and Nele, V and Che, J and Booth, MA and Doutch, JJ and Stevens, M},
doi = {10.1039/D0TB01546F},
journal = {Journal of Materials Chemistry B},
pages = {8894--8907},
title = {Tuneable peptide cross-linked nanogels for enzyme-triggered protein delivery},
url = {http://dx.doi.org/10.1039/D0TB01546F},
volume = {8},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Many diseases are associated with the dysregulated activity of enzymes, such as matrixmetalloproteinases (MMPs). This dysregulation can be leveraged in drug delivery to achieve disease- orsite-specific cargo release. Self-assembled polymeric nanoparticles are versatile drug carrier materialsdue to the accessible diversity of polymer chemistry. However, efficient loading of sensitive cargo, suchas proteins, and introducing functional enzyme-responsive behaviour remain challenging. Herein,peptide-crosslinked, temperature-sensitive nanogels for protein delivery were designed to respond toMMP-7, which is overexpressed in many pathologies including cancer and inflammatory diseases. Theincorporation of N-cyclopropylacrylamide (NCPAM) into N-isopropylacrylamide (NIPAM)-basedcopolymers enabled us to tune the polymer lower critical solution temperature from 33 to 44 1C,allowing the encapsulation of protein cargo and nanogel-crosslinking at slightly elevated temperatures.This approach resulted in nanogels that were held together by MMP-sensitive peptides for enzymespecificprotein delivery. We employed a combination of cryogenic transmission electron microscopy(cryo-TEM), dynamic light scattering (DLS), small angle neutron scattering (SANS), and fluorescencecorrelation spectroscopy (FCS) to precisely decipher the morphology, self-assembly mechanism,enzyme-responsiveness, and model protein loading/release properties of our nanogel platform. Simplevariation of the peptide linker sequence and combining multiple different crosslinkers will enable us toadjust our platform to target specific diseases in the future.
AU  - Massi,L
AU  - Najer,A
AU  - Chapman,R
AU  - Spicer,C
AU  - Nele,V
AU  - Che,J
AU  - Booth,MA
AU  - Doutch,JJ
AU  - Stevens,M
DO  - 10.1039/D0TB01546F
EP  - 8907
PY  - 2020///
SN  - 2050-750X
SP  - 8894
TI  - Tuneable peptide cross-linked nanogels for enzyme-triggered protein delivery
T2  - Journal of Materials Chemistry B
UR  - http://dx.doi.org/10.1039/D0TB01546F
UR  - https://pubs.rsc.org/en/content/articlelanding/2020/TB/D0TB01546F#!divAbstract
UR  - http://hdl.handle.net/10044/1/82302
VL  - 8
ER  -
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