Targeted Cascade Therapy with Multifunctional Nanovesicles Engineered from Synergistic Antibacterial Agents for Precision Treatment of Multidrug-Resistant Infections and Biofilms.

IF 26.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yiyu Gong,Min Lin,Dongze Li,Rui Yao,Guojing Zhang,Jing Sun,Xuesi Chen
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Abstract

Multidrug-resistant (MDR) Staphylococcus aureus (S. aureus), classified as a high-priority tier II pathogen, poses a glowing threat to global health. Single-mode antibacterial approaches often fall short of achieving optimal effects, necessitating the development of combination therapies. To address these challenges, pH-responsive antibacterial nanovesicles, termed DAClLy, are developed by integrating targeting ligand and multiple antimicrobial agents with complementary modes of action to target MDR bacteria with enhanced efficacy while minimizing adverse effects. DAClLy are engineered through the complexation of sulfonium-ion-bearing antibacterial polypeptoids, and primary amine-containing polypeptoids modified with 2,3-dimethyl maleic anhydride, encapsulating lysostaphin, a bacteriolytic enzyme. Upon reaching the acidic microenvironment of bacterial infections, the DAClLy vesicles disassemble, releasing their antimicrobial components. The released lysostaphin degrades bacterial cell walls, while the polypeptoids synergistically disrupt bacterial membranes, resulting in a multi-action bactericidal effect. This synergistic mechanism demonstrates remarkable efficacy against MDR S. aureus, including its resilient biofilm formations. In vivo studies have shown that the DAClLy vesicles exhibit potent antibacterial activity against MDR S. aureus-induced skin and lung infections. The nanovesicles effectively penetrate the lung mucus barrier, addressing both surface-level and deep-tissue infections. By integrating multiple strategies, DAClLy offers a promising therapeutic strategy to combat MDR pathogens across diverse tissue contexts.
协同抗菌剂设计的多功能纳米囊泡靶向级联治疗用于精确治疗多重耐药感染和生物膜。
耐多药(MDR)金黄色葡萄球菌(金黄色葡萄球菌)被列为高度优先的第二级病原体,对全球健康构成巨大威胁。单模抗菌方法往往达不到最佳效果,需要开发联合治疗。为了解决这些挑战,ph响应型抗菌纳米囊泡,称为dacly,通过整合靶向配体和多种具有互补作用模式的抗菌药物来靶向耐多药细菌,提高疗效,同时最大限度地减少不良反应。dacly是由含硫离子的抗菌多肽和2,3-二甲基马来酸酐修饰的含伯胺的多肽络合而成的,这些多肽包裹着溶葡萄球菌酶(一种溶菌酶)。一旦到达细菌感染的酸性微环境,dacly囊泡就会分解,释放出它们的抗菌成分。释放的溶葡萄球菌蛋白降解细菌细胞壁,而多肽则协同破坏细菌膜,产生多效杀菌作用。这种协同机制显示了对耐多药金黄色葡萄球菌的显著疗效,包括其弹性生物膜的形成。体内研究表明,dacly囊泡对耐多药金黄色葡萄球菌引起的皮肤和肺部感染表现出强大的抗菌活性。纳米囊泡有效地穿透肺部粘液屏障,解决表面和深层组织感染。通过整合多种策略,dacly提供了一种有前途的治疗策略,可以在不同的组织环境中对抗MDR病原体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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