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Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria

[Image: see text] 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 versa...

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Autores principales: Potter, Michael, Najer, Adrian, Klöckner, Anna, Zhang, Shaodong, Holme, Margaret N., Nele, Valeria, Che, Junyi, Massi, Lucia, Penders, Jelle, Saunders, Catherine, Doutch, James J., Edwards, Andrew M., Ces, Oscar, Stevens, Molly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760217/
https://www.ncbi.nlm.nih.gov/pubmed/33290039
http://dx.doi.org/10.1021/acsnano.0c07459
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author Potter, Michael
Najer, Adrian
Klöckner, Anna
Zhang, Shaodong
Holme, Margaret N.
Nele, Valeria
Che, Junyi
Massi, Lucia
Penders, Jelle
Saunders, Catherine
Doutch, James J.
Edwards, Andrew M.
Ces, Oscar
Stevens, Molly M.
author_facet Potter, Michael
Najer, Adrian
Klöckner, Anna
Zhang, Shaodong
Holme, Margaret N.
Nele, Valeria
Che, Junyi
Massi, Lucia
Penders, Jelle
Saunders, Catherine
Doutch, James J.
Edwards, Andrew M.
Ces, Oscar
Stevens, Molly M.
author_sort Potter, Michael
collection PubMed
description [Image: see text] 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 H(2)O(2) 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.
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spelling pubmed-77602172020-12-28 Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria Potter, Michael Najer, Adrian Klöckner, Anna Zhang, Shaodong Holme, Margaret N. Nele, Valeria Che, Junyi Massi, Lucia Penders, Jelle Saunders, Catherine Doutch, James J. Edwards, Andrew M. Ces, Oscar Stevens, Molly M. ACS Nano [Image: see text] 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 H(2)O(2) 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. American Chemical Society 2020-12-08 2020-12-22 /pmc/articles/PMC7760217/ /pubmed/33290039 http://dx.doi.org/10.1021/acsnano.0c07459 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Potter, Michael
Najer, Adrian
Klöckner, Anna
Zhang, Shaodong
Holme, Margaret N.
Nele, Valeria
Che, Junyi
Massi, Lucia
Penders, Jelle
Saunders, Catherine
Doutch, James J.
Edwards, Andrew M.
Ces, Oscar
Stevens, Molly M.
Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria
title Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria
title_full Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria
title_fullStr Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria
title_full_unstemmed Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria
title_short Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria
title_sort controlled dendrimersome nanoreactor system for localized hypochlorite-induced killing of bacteria
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760217/
https://www.ncbi.nlm.nih.gov/pubmed/33290039
http://dx.doi.org/10.1021/acsnano.0c07459
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