College of animal science and technology, Northeast Agricultural University, Harbin 150030, China.
ACS Nano. 2024 Sep 17;18(37):25446-25464. doi: 10.1021/acsnano.4c03669. Epub 2024 Sep 6.
The alarming rise in global antimicrobial resistance underscores the urgent need for effective antibacterial drugs. Drawing inspiration from the bacterial-entrapment mechanism of human defensin 6, we have fabricated biomimetic peptide nanonets composed of multiple functional fragments for bacterial eradication. These biomimetic peptide nanonets are designed to address antimicrobial resistance challenges through a dual-approach strategy. First, the resulting nanofibrous networks trap bacteria and subsequently kill them by loosening the membrane structure, dissipating proton motive force, and causing multiple metabolic perturbations. Second, these trapped bacterial clusters reactivate macrophages to scavenge bacteria through enhanced chemotaxis and phagocytosis via the PI3K-AKT signaling pathway and ECM-receptor interaction. results have proven that treatment with biomimetic peptide nanonets can alleviate systemic bacterial infections without causing noticeable systemic toxicity. As anticipated, the proposed strategy can address stubborn infections by entrapping bacteria and awakening antibacterial immune responses. This approach might serve as a guide for the design of bioinspired materials for future clinical applications.
全球抗菌药物耐药性的惊人上升凸显了急需有效抗菌药物的紧迫性。受人类防御素 6 的细菌捕获机制的启发，我们设计了由多个功能片段组成的仿生肽纳米网，用于杀菌。这些仿生肽纳米网旨在通过双管齐下的策略来应对抗菌药物耐药性的挑战。首先，生成的纳米纤维网络捕获细菌，然后通过松弛膜结构、耗散质子动力和引起多种代谢紊乱来杀死细菌。其次，这些被捕获的细菌簇通过增强趋化性和吞噬作用来重新激活巨噬细胞，通过 PI3K-AKT 信号通路和细胞外基质-受体相互作用来吞噬细菌。结果表明，使用仿生肽纳米网治疗可以减轻全身细菌感染，而不会引起明显的全身毒性。可以预期，该策略通过捕获细菌和唤醒抗菌免疫反应可以解决顽固的感染。该方法可以为未来临床应用的仿生材料设计提供指导。
