Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do 57922, Republic of Korea.
ACS Appl Mater Interfaces. 2020 Dec 9;12(49):54306-54315. doi: 10.1021/acsami.0c13083. Epub 2020 Nov 25.
Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria. Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells. Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications. Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms. In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents. These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.
由耐多药细菌引起的传染病是医学上的一个难题，因为全球致病菌的耐药性呈上升趋势。尽管在抗生素和抗菌剂的开发方面做出了巨大努力，但仍非常需要开发一种策略，以便早期检测细菌感染并有效且同时消灭细菌。各种生物体的先天免疫系统会产生抗菌肽，这些肽对哺乳动物细胞的细胞毒性很小，但却能杀死广泛的细菌。因此，抗菌肽最近作为传统抗生素在抗菌药物中的替代品引起了越来越多的关注。在这里，我们报告了一种新的抗菌剂家族，它是由嵌合抗菌脂肽（DSPE-HnMc）和两亲可生物降解聚合物自组装而成的。HnMc 胶束可以有效地与细菌膜结合，杀死广谱细菌和细菌生物膜。在耐药菌感染的小鼠模型研究中，HnMc 胶束可以高特异性地靶向细菌感染，还可以有效地杀死耐药菌，这表明 HnMc 胶束作为成像和靶向抗菌剂具有巨大的潜力。这些发现还为基于抗菌肽的纳米医学用于检测和治疗细菌感染提供了新的见解。
