Nabawy Ahmed, Chattopadhyay Aritra Nath, Makabenta Jessa Marie V, Hassan Muhammad Aamir, Yang Junwhee, Park Jungmi, Jiang Mingdi, Jeon Taewon, Im Jungkyun, Rotello Vincent M
Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA.
Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 230 Stockbridge Road, Amherst, MA, 01003, USA.
Biomaterials. 2025 May;316:123015. doi: 10.1016/j.biomaterials.2024.123015. Epub 2024 Dec 15.
Biofilm-associated infections arising from antibiotic-resistant bacteria pose a critical challenge to global health. We report the generation of a library of cationic conjugated poly(phenylene ethynylene) (PPE) polymers featuring trimethylammonium terminated sidechains with tunable hydrophobicity. Screening of the library identified an amphiphilic polymer with a C hydrophobic spacer as the polymer with the highest antimicrobial efficacy against biofilms in the dark with excellent selectivity. These polymers are highly fluorescent, allowing label-free monitoring of polymer-bacteria/biofilm interactions. The amphiphilic conjugated polymer penetrated the biofilm matrix in vitro and eradicated resident bacteria through membrane disruption. This C polymer was likewise effective in an in vivo murine model of antibiotic-resistant wound biofilm infections, clearing >99.9 % of biofilm colonies and efficient alleviation of biofilm-associated inflammation. The results demonstrate the therapeutic potential of the fluorescent conjugated polymer platform as a multi-modal antimicrobial and imaging tool, surpassing conventional antimicrobial strategies against resilient biofilm infection.
由抗生素耐药细菌引起的生物膜相关感染对全球健康构成了严峻挑战。我们报告了一个阳离子共轭聚（亚苯基乙炔）（PPE）聚合物库的生成，该聚合物具有带有可调节疏水性的三甲基铵封端侧链。对该库的筛选确定了一种具有C疏水间隔基的两亲性聚合物，它是在黑暗中对生物膜具有最高抗菌效力且具有出色选择性的聚合物。这些聚合物具有高荧光性，能够对聚合物 - 细菌/生物膜相互作用进行无标记监测。这种两亲性共轭聚合物在体外穿透生物膜基质，并通过膜破坏消除驻留细菌。这种C聚合物在抗生素耐药伤口生物膜感染的体内小鼠模型中同样有效，清除了>99.9%的生物膜菌落，并有效减轻了生物膜相关炎症。结果表明，荧光共轭聚合物平台作为一种多模态抗菌和成像工具具有治疗潜力，超越了针对顽固生物膜感染的传统抗菌策略。
