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Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators

[Image: see text] Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities in the form of biofilms, present a strong challenge to therapeutic treatment due to resistance to conventional antimicrobial therapies. Lipo...

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Autores principales: Kluzek, Monika, Oppenheimer-Shaanan, Yaara, Dadosh, Tali, Morandi, Mattia I., Avinoam, Ori, Raanan, Calanit, Goldsmith, Moshe, Goldberg, Ronit, Klein, Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620068/
https://www.ncbi.nlm.nih.gov/pubmed/36018573
http://dx.doi.org/10.1021/acsnano.2c04232
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author Kluzek, Monika
Oppenheimer-Shaanan, Yaara
Dadosh, Tali
Morandi, Mattia I.
Avinoam, Ori
Raanan, Calanit
Goldsmith, Moshe
Goldberg, Ronit
Klein, Jacob
author_facet Kluzek, Monika
Oppenheimer-Shaanan, Yaara
Dadosh, Tali
Morandi, Mattia I.
Avinoam, Ori
Raanan, Calanit
Goldsmith, Moshe
Goldberg, Ronit
Klein, Jacob
author_sort Kluzek, Monika
collection PubMed
description [Image: see text] Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities in the form of biofilms, present a strong challenge to therapeutic treatment due to resistance to conventional antimicrobial therapies. Liposomes can provide a versatile drug-vector strategy for biofilm treatment, but are limited by the need to balance colloidal stability with biofilm penetration. We have discovered a liposomic functionalization strategy, using membrane-embedded moieties of poly[2-(methacryloyloxy)ethyl phosphorylcholine], pMPC, that overcomes this limitation. Such pMPCylation results in liposomic stability equivalent to current functionalization strategies (mostly PEGylation, the present gold-standard), but with strikingly improved cellular uptake and cargo conveyance. Fluorimetry, cryo-electron, and fluorescence microscopies reveal a far-enhanced antibiotic delivery to model Pseudomonas aeruginosa biofilms by pMPC-liposomes, followed by faster cytosolic cargo release, resulting in significantly greater biofilm eradication than either PEGylation or free drug. Moreover, this combination of techniques uncovers the molecular mechanism underlying the enhanced interaction with bacteria, indicating it arises from bridging by divalent ions of the zwitterionic groups on the pMPC moieties to the negatively charged lipopolysaccharide chains emanating from the bacterial membranes. Our results point to pMPCylation as a transformative strategy for liposomal functionalization, leading to next-generation delivery systems for biofilm treatment.
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spelling pubmed-96200682022-11-01 Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators Kluzek, Monika Oppenheimer-Shaanan, Yaara Dadosh, Tali Morandi, Mattia I. Avinoam, Ori Raanan, Calanit Goldsmith, Moshe Goldberg, Ronit Klein, Jacob ACS Nano [Image: see text] Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities in the form of biofilms, present a strong challenge to therapeutic treatment due to resistance to conventional antimicrobial therapies. Liposomes can provide a versatile drug-vector strategy for biofilm treatment, but are limited by the need to balance colloidal stability with biofilm penetration. We have discovered a liposomic functionalization strategy, using membrane-embedded moieties of poly[2-(methacryloyloxy)ethyl phosphorylcholine], pMPC, that overcomes this limitation. Such pMPCylation results in liposomic stability equivalent to current functionalization strategies (mostly PEGylation, the present gold-standard), but with strikingly improved cellular uptake and cargo conveyance. Fluorimetry, cryo-electron, and fluorescence microscopies reveal a far-enhanced antibiotic delivery to model Pseudomonas aeruginosa biofilms by pMPC-liposomes, followed by faster cytosolic cargo release, resulting in significantly greater biofilm eradication than either PEGylation or free drug. Moreover, this combination of techniques uncovers the molecular mechanism underlying the enhanced interaction with bacteria, indicating it arises from bridging by divalent ions of the zwitterionic groups on the pMPC moieties to the negatively charged lipopolysaccharide chains emanating from the bacterial membranes. Our results point to pMPCylation as a transformative strategy for liposomal functionalization, leading to next-generation delivery systems for biofilm treatment. American Chemical Society 2022-08-26 2022-10-25 /pmc/articles/PMC9620068/ /pubmed/36018573 http://dx.doi.org/10.1021/acsnano.2c04232 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Kluzek, Monika
Oppenheimer-Shaanan, Yaara
Dadosh, Tali
Morandi, Mattia I.
Avinoam, Ori
Raanan, Calanit
Goldsmith, Moshe
Goldberg, Ronit
Klein, Jacob
Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
title Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
title_full Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
title_fullStr Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
title_full_unstemmed Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
title_short Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators
title_sort designer liposomic nanocarriers are effective biofilm eradicators
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620068/
https://www.ncbi.nlm.nih.gov/pubmed/36018573
http://dx.doi.org/10.1021/acsnano.2c04232
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