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{Potter:2020:10.1021/acsnano.0c07459,
author = {Potter, M and Najer, A and Kloeckner, A and Zhang, S and Holme, MN and Nele, V and Che, J and Penders, J and Saunders, C and Doutch, JJ and Edwards, A and Ces, O and Stevens, M},
doi = {10.1021/acsnano.0c07459},
journal = {ACS Nano},
pages = {17333--17353},
title = {Controlled dendrimersome nanoreactor system for localised hypochlorite-induced killing of bacteria},
url = {http://dx.doi.org/10.1021/acsnano.0c07459},
volume = {14},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Antibiotic resistance is a serious global health problem necessitating new bactericidal approaches such as nanomedicines. Dendrimersomes (DSs) have recently become a valuable alternative nanocarrier to polymersomes and liposomes due to their molecular definition and synthetic versatility. Despite this, their biomedical application is still in its infancy. Inspired by the localized antimicrobial function of neutrophil phagosomes and the versatility of DSs, a simple three-component DS-based nanoreactor with broad-spectrum bactericidal activity is presented. This was achieved by encapsulation of glucose oxidase (GOX) and myeloperoxidase (MPO) within DSs (GOX-MPO-DSs), self-assembled from an amphiphilic Janus dendrimer, that possesses a semipermeable membrane. By external addition of glucose to GOX-MPO-DS, the production of hypochlorite (−OCl), a highly potent antimicrobial, by the enzymatic cascade was demonstrated. This cascade nanoreactor yielded a potent bactericidal effect against two important multidrug resistant pathogens, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), not observed for H2O2 producing nanoreactors, GOX-DS. The production of highly reactive species such as –OCl represents a harsh bactericidal approach that could also be cytotoxic to mammalian cells. This necessitates the development of strategies for activating –OCl production in a localized manner in response to a bacterial stimulus. One option of locally releasing sufficient amounts of substrate using a bacterial trigger (released toxins) was demonstrated with lipidic glucose-loaded giant unilamellar vesicles (GUVs), envisioning, e.g., implant surface modification with nanoreactors and GUVs for localized production of bactericidal agents in the presence of bacterial growth.
AU  - Potter,M
AU  - Najer,A
AU  - Kloeckner,A
AU  - Zhang,S
AU  - Holme,MN
AU  - Nele,V
AU  - Che,J
AU  - Penders,J
AU  - Saunders,C
AU  - Doutch,JJ
AU  - Edwards,A
AU  - Ces,O
AU  - Stevens,M
DO  - 10.1021/acsnano.0c07459
EP  - 17353
PY  - 2020///
SN  - 1936-0851
SP  - 17333
TI  - Controlled dendrimersome nanoreactor system for localised hypochlorite-induced killing of bacteria
T2  - ACS Nano
UR  - http://dx.doi.org/10.1021/acsnano.0c07459
UR  - https://pubs.acs.org/doi/10.1021/acsnano.0c07459
UR  - http://hdl.handle.net/10044/1/84960
VL  - 14
ER  -
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