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载有两亲性多肽和抗生素的磁性丝素纳米球用于生物膜清除。

Magnetic silk fibroin nanospheres loaded with amphiphilic polypeptides and antibiotics for biofilm eradication.

机构信息

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science and Laboratory of Advanced Materials, Fudan University, Shanghai 200438, P.R. China.

出版信息

Biomater Sci. 2024 Oct 8;12(20):5337-5348. doi: 10.1039/d4bm01065e.

DOI:10.1039/d4bm01065e
PMID:39248307
Abstract

The eradication of established biofilms is a highly challenging task, due to the protective barrier effect of extracellular polymeric substances (EPS) and the presence of persister cells. Both increased drug permeability and elimination of persister cells are essential for the eradication of biofilms. Here, magnetic silk fibroin nanospheres loaded with antibiotics and host defense peptide (HDP) mimics (MPSN/S@P) were developed to demonstrate a new strategy for biofilm eradication. As an HDP mimic, an amphiphilic polypeptide containing 90% L-lysine and 10% L-valine (LysVal) was selected for loading onto magnetic silk fibroin nanospheres electrostatic interactions. LysVal exhibited excellent antibacterial activities against both planktonic and persister cells of (). As a representative of the hydrophobic drug, spiramycin (SPM) was conveniently embedded into the β-sheet domain during the self-assembly process of silk fibroin. The sustained release of SPM during biofilm eradication enhanced the antibacterial efficacy of MPSN/S@P. The antibacterial test demonstrated that the extract from the MPSN/S@P suspension can kill both planktonic and persister cells of , as well as inhibiting biofilm formation. Importantly, with the assistance of magnetic guidance and photothermal effects derived from FeO nanoparticles (FeO NPs), over 92% of bacteria in the biofilm were killed by MPSN/S@P, indicating the successful eradication of mature biofilms. The simple preparation method, integration of photothermal and magnetic responsiveness, and persister cell killing functions of MPSN/S@P provide an accessible strategy and illustrative paradigm for efficient biofilm eradication.

摘要

消除已建立的生物膜是一项极具挑战性的任务,这是由于细胞外聚合物(EPS)的保护屏障效应和持久细胞的存在。增加药物通透性和消除持久细胞对于生物膜的消除都是必不可少的。在这里,载有抗生素和宿主防御肽(HDP)模拟物的磁性丝素纳米球(MPSN/S@P)被开发出来,以展示一种新的生物膜消除策略。作为 HDP 模拟物,选择了一种含有 90%赖氨酸和 10%缬氨酸(LysVal)的两亲性多肽,通过静电相互作用加载到磁性丝素纳米球上。LysVal 对()浮游细胞和持久细胞均表现出优异的抗菌活性。作为疏水性药物的代表,螺旋霉素(SPM)在丝素蛋白自组装过程中方便地嵌入β-折叠结构域。在生物膜消除过程中,SPM 的持续释放增强了 MPSN/S@P 的抗菌功效。抗菌试验表明,MPSN/S@P 悬浮液的提取物可以杀死()浮游细胞和持久细胞,并抑制生物膜形成。重要的是,在 FeO 纳米粒子(FeO NPs)产生的磁引导和光热效应的辅助下,MPSN/S@P 可以杀死生物膜中超过 92%的细菌,表明成熟生物膜的成功消除。MPSN/S@P 的简单制备方法、光热和磁响应的集成以及持久细胞杀伤功能为高效生物膜消除提供了一种可行的策略和示范。

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