Switchable supramolecular polycationic assemblies for tunable antibacterial strategies against antibiotic resistance

IF 7.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Chemical Science Pub Date : 2025-10-07 DOI:10.1039/d5sc05035a

Jia Chen, Xueqian Wang, Mengrui Zhang, Xue Wang, Ran Wang, Xinxing Lyu, Yunjian Xu, Xintian Shao, Luling Wu, Tony D. James

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引用次数: 0

Abstract

Bacterial resistance significantly hampers the efficacy of antibiotics in eradicating pathogens and treating infections. Here, we introduce an Adaptive Cationic Therapeutic Integrated (ACTI) system, a design strategy integrating pyridinium cationic membrane disruption and tunable antibacterial activity to address this challenge. ACTI leverages the assembled hyper-enriched cationic domains to enhance the destruction of bacterial membranes, while also enabling the on-demand deactivation of antibacterial activity through disassembly, thereby safeguarding biocompatibility. Additionally, ACTI facilitates the photodynamic inactivation of negatively charged photosensitizers (TPPS) by promoting the interaction between the photosensitizer and bacteria as well as aiding the transport of singlet oxygen. ACTI-loaded photosensitizers (TPPS@ACTI) exhibited potent antibacterial activity (>99% pathogen elimination) against methicillin-resistant S. aureus (MRSA) and E. coli in vitro, and the antibacterial efficacy was further validated using an MRSA-infected murine wound model. ACTI establishes a paradigm shift for the design of tunable antimicrobials that balance potency and biosafety in complex biological environments.

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可切换的超分子聚阳离子组合物可调节抗菌策略对抗抗生素耐药性

细菌耐药性严重阻碍了抗生素根除病原体和治疗感染的功效。在这里，我们介绍了一种自适应阳离子治疗集成（ACTI）系统，一种整合了吡啶阳离子膜破坏和可调抗菌活性的设计策略来解决这一挑战。ACTI利用组装的超富集阳离子结构域来增强对细菌膜的破坏，同时也可以通过拆卸来按需灭活抗菌活性，从而保护生物相容性。此外，ACTI通过促进光敏剂与细菌之间的相互作用以及帮助单线态氧的运输，促进带负电荷的光敏剂（TPPS）的光动力学失活。负载act的光敏剂（TPPS@ACTI）在体外对耐甲氧西林金黄色葡萄球菌（MRSA）和大肠杆菌表现出强大的抗菌活性（>；99%的病原体消除），抗菌效果通过MRSA感染的小鼠伤口模型得到进一步验证。ACTI为可调抗菌剂的设计建立了一个范式转变，在复杂的生物环境中平衡效力和生物安全性。

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来源期刊

Chemical Science CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

14.40

自引率

4.80%

发文量

1352

审稿时长

2.1 months

期刊介绍： Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.