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Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms
BACKGROUND: Biofilm formation is one of the main reasons for persistent bacterial infections. Recently, pH-sensitive copolymers have fascinated incredible attention to tackle biofilm-related infections. However, the proper incorporation of pH-sensitive segments in the polymer chains, which could sig...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344171/ https://www.ncbi.nlm.nih.gov/pubmed/34362397 http://dx.doi.org/10.1186/s12951-021-00980-8 |
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author | Guo, Rong Li, Keke Tian, Baocheng Wang, Changrong Chen, Xiangjun Jiang, Xinyu He, Huayu Hong, Wei |
author_facet | Guo, Rong Li, Keke Tian, Baocheng Wang, Changrong Chen, Xiangjun Jiang, Xinyu He, Huayu Hong, Wei |
author_sort | Guo, Rong |
collection | PubMed |
description | BACKGROUND: Biofilm formation is one of the main reasons for persistent bacterial infections. Recently, pH-sensitive copolymers have fascinated incredible attention to tackle biofilm-related infections. However, the proper incorporation of pH-sensitive segments in the polymer chains, which could significantly affect the biofilms targeting ability, has not been particularly investigated. Herein, we synthesized three types of pH-sensitive copolymers based on poly (β-amino ester) (PAE), poly (lactic-co-glycolic acid) (PLA) and polyethylene glycol (PEG), PAE-PLA-mPEG (A-L-E), PLA-PAE-mPEG (L-A-E) and PLA-PEG-PAE (L-E-A) to address this issue. RESULTS: The three copolymers could self-assemble into micelles (M(A-L-E), M(L-A-E) and M(L-E-A)) in aqueous medium. Compared with M(A-L-E) and M(L-A-E), placing the PAE at the distal PEG end of PLA-PEG to yield PLA-PEG-PAE (M(L-E-A)) was characterized with proper triggering pH, fully biofilm penetration, and high cell membrane binding affinity. Further loaded with Triclosan (TCS), M(L-E-A)/TCS could efficiently kill the bacteria either in planktonic or biofilm mode. We reasoned that PAE segments would be preferentially placed near the surface and distant from the hydrophobic PLA segments. This would increase the magnitude of surface charge-switching capability, as the cationic PAE(+) would easily disassociate from the inner core without conquering the additional hydrophobic force arising from covalent linkage with PLA segments, and rapidly rise to the outermost layer of the micellar surface due to the relative hydrophilicity. This was significant in that it could enable the micelles immediately change its surface charge where localized acidity occurred, and efficiently bind themselves to the bacterial surface where they became hydrolyzed by bacterial lipases to stimulate release of encapsulated TCS even a relatively short residence time to prevent rapid wash-out. In vivo therapeutic performance of M(L-E-A)/TCS was evaluated on a classical biofilm infection model, implant-related biofilm infection. The result suggested that M(L-E-A)/TCS was effective for the treatment of implant-related biofilm infection, which was proved by the efficient clearance of biofilm-contaminated catheters and the recovery of surrounding infected tissues. CONCLUSIONS: In summary, elaboration on the architecture of pH-sensitive copolymers was the first step to target biofilm. The M(L-E-A) structure may represent an interesting future direction in the treatment of biofilm-relevant infections associated with acidity. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00980-8. |
format | Online Article Text |
id | pubmed-8344171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83441712021-08-09 Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms Guo, Rong Li, Keke Tian, Baocheng Wang, Changrong Chen, Xiangjun Jiang, Xinyu He, Huayu Hong, Wei J Nanobiotechnology Research BACKGROUND: Biofilm formation is one of the main reasons for persistent bacterial infections. Recently, pH-sensitive copolymers have fascinated incredible attention to tackle biofilm-related infections. However, the proper incorporation of pH-sensitive segments in the polymer chains, which could significantly affect the biofilms targeting ability, has not been particularly investigated. Herein, we synthesized three types of pH-sensitive copolymers based on poly (β-amino ester) (PAE), poly (lactic-co-glycolic acid) (PLA) and polyethylene glycol (PEG), PAE-PLA-mPEG (A-L-E), PLA-PAE-mPEG (L-A-E) and PLA-PEG-PAE (L-E-A) to address this issue. RESULTS: The three copolymers could self-assemble into micelles (M(A-L-E), M(L-A-E) and M(L-E-A)) in aqueous medium. Compared with M(A-L-E) and M(L-A-E), placing the PAE at the distal PEG end of PLA-PEG to yield PLA-PEG-PAE (M(L-E-A)) was characterized with proper triggering pH, fully biofilm penetration, and high cell membrane binding affinity. Further loaded with Triclosan (TCS), M(L-E-A)/TCS could efficiently kill the bacteria either in planktonic or biofilm mode. We reasoned that PAE segments would be preferentially placed near the surface and distant from the hydrophobic PLA segments. This would increase the magnitude of surface charge-switching capability, as the cationic PAE(+) would easily disassociate from the inner core without conquering the additional hydrophobic force arising from covalent linkage with PLA segments, and rapidly rise to the outermost layer of the micellar surface due to the relative hydrophilicity. This was significant in that it could enable the micelles immediately change its surface charge where localized acidity occurred, and efficiently bind themselves to the bacterial surface where they became hydrolyzed by bacterial lipases to stimulate release of encapsulated TCS even a relatively short residence time to prevent rapid wash-out. In vivo therapeutic performance of M(L-E-A)/TCS was evaluated on a classical biofilm infection model, implant-related biofilm infection. The result suggested that M(L-E-A)/TCS was effective for the treatment of implant-related biofilm infection, which was proved by the efficient clearance of biofilm-contaminated catheters and the recovery of surrounding infected tissues. CONCLUSIONS: In summary, elaboration on the architecture of pH-sensitive copolymers was the first step to target biofilm. The M(L-E-A) structure may represent an interesting future direction in the treatment of biofilm-relevant infections associated with acidity. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00980-8. BioMed Central 2021-08-06 /pmc/articles/PMC8344171/ /pubmed/34362397 http://dx.doi.org/10.1186/s12951-021-00980-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Guo, Rong Li, Keke Tian, Baocheng Wang, Changrong Chen, Xiangjun Jiang, Xinyu He, Huayu Hong, Wei Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
title | Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
title_full | Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
title_fullStr | Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
title_full_unstemmed | Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
title_short | Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
title_sort | elaboration on the architecture of ph-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344171/ https://www.ncbi.nlm.nih.gov/pubmed/34362397 http://dx.doi.org/10.1186/s12951-021-00980-8 |
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