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用于协同根除细菌生物膜的载一氧化氮抗菌聚合物

Nitric Oxide-Loaded Antimicrobial Polymer for the Synergistic Eradication of Bacterial Biofilm.

作者信息

Namivandi-Zangeneh Rashin, Sadrearhami Zahra, Bagheri Ali, Sauvage-Nguyen Maeva, Ho Kitty Ka Kit, Kumar Naresh, Wong Edgar H H, Boyer Cyrille

机构信息

Centre for Advanced Macromolecular Design (CAMD) and Australian Centre for NanoMedicine (ACN), School of Chemical Engineering, UNSW Australia, Sydney, NSW 2052, Australia.

Chimie ParisTech, 11 Rue Pierre et Marie Curie, Paris, 75005, France.

出版信息

ACS Macro Lett. 2018 May 15;7(5):592-597. doi: 10.1021/acsmacrolett.8b00190. Epub 2018 May 4.

Abstract

Bacterial biofilms are often difficult to treat and represent the main cause of chronic and recurrent infections. In this study, we report the synthesis of a novel antimicrobial/antibiofilm polymer that consists of biocompatible oligoethylene glycol, hydrophobic ethylhexyl, cationic primary amine, and nitric oxide (NO)-releasing functional groups. The NO-loaded polymer has dual-action capability as it can release NO which triggers the dispersion of biofilm, whereas the polymer can induce bacteria cell death via membrane wall disruption. By functionalizing the polymers with NO, we observed a synergistic effect in biofilm dispersal, planktonic and biofilm killing activities against . The NO-loaded polymer results in 80% reduction in biofilm biomass and kills >99.999% of planktonic and biofilm cells within 1 h of treatment at a polymer concentration of 64 μg mL. To achieve this synergistic effect, it is imperative that the NO donors and antimicrobial polymer exist as a single chemical entity, instead of a cocktail physical mixture of two individual components. The excellent antimicrobial/antibiofilm activity of this dual-action polymer suggests the advantages of combination therapy in combating bacterial biofilms.

摘要

细菌生物膜往往难以治疗,是慢性和复发性感染的主要原因。在本研究中,我们报告了一种新型抗菌/抗生物膜聚合物的合成,该聚合物由生物相容性低聚乙二醇、疏水性乙基己基、阳离子伯胺和一氧化氮(NO)释放官能团组成。负载NO的聚合物具有双重作用能力,因为它可以释放NO,从而引发生物膜的分散,而该聚合物可以通过破坏细胞膜壁诱导细菌细胞死亡。通过用NO对聚合物进行功能化,我们观察到在生物膜分散、对浮游菌和生物膜的杀灭活性方面存在协同效应。负载NO的聚合物在聚合物浓度为64μg/mL的情况下,处理1小时后可使生物膜生物量减少80%,并杀死>99.999%的浮游菌和生物膜细胞。为了实现这种协同效应,NO供体和抗菌聚合物必须作为单一化学实体存在,而不是两种单独成分的混合物理混合物。这种双功能聚合物优异的抗菌/抗生物膜活性表明联合疗法在对抗细菌生物膜方面的优势。

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