自组装纳米抗菌肽的设计策略及应用

Design strategy and application of self-assembled nano-antimicrobial peptides

细菌感染,特别是耐药菌感染,是人类公共卫生的最大威胁之一.与传统抗生素相比,抗菌肽以其多模式作用机制和较低的耐药性风险,展现出显著优势.尽管抗菌肽存在稳定性差、细胞毒性高等问题,限制了其临床应用,但抗菌肽自组装形成纳米结构在很大程度克服了这些限制,并展现出极大的治疗潜力.本综述对抗菌肽自组装纳米材料的设计策略及其在治疗细菌感染方面的应用进行了系统总结,重点介绍了基于两亲性氨基酸非共价力驱动和化学修饰形成自组装抗菌肽的设计方法,最后描述了自组装纳米抗菌肽在腹腔感染、皮肤感染、肺部感染中的治疗潜力,以及在其他领域的应用价值.期望该综述可为该领域的进一步研究提供指导,以促进新型抑菌剂的发展.

Bacterial infections are a major global health problem,and the advent of antibiotics marked the golden age of treating bacterial infections,saving hundreds of millions of lives.However,the mechanism of action of conventional antibiotics is often limited to targeting specific physiological or biochemical processes in bacteria.As a result,this single target of action is easily circumvented by bacteria through evolution,leading to the emergence of resistance.The ability of drug-resistant bacteria to evade the action of conventional antibiotics makes the treatment of infections even more challenging.Antimicrobial peptides(also known as host defence peptides)are a new approach to treating bacterial infections.They have a multimodal mechanism of action and are capable of eliminating pathogens from multiple targets.This multifaceted approach not only enhances the antimicrobial efficacy of antimicrobial peptides,but also makes it more difficult for bacteria to develop resistance to specific antimicrobial peptides.This property gives antimicrobial peptides great potential against drug-resistant bacteria.However,antimicrobial peptides have encountered a number of obstacles in their practical application.Their unstable activity,poor protease stability in vivo,high cytotoxicity,and short half-life limit their clinical applications.To address these limitations,self-assembly of antimicrobial peptides is an effective approach.Self-assembly of antimicrobial peptides is a novel nanomedicine technology that closely links the activity of antimicrobial peptides with nanostructures.The self-assembly process of antimicrobial peptides was investigated through a bottom-up design strategy.Self-assembly of antimicrobial peptides was shown to reduce renal clearance,enhance protease stability,prolong half-life and improve targeting selectivity.Another advantage of self-assembled antimicrobial peptides is the design flexibility,which allows modification of the functional groups as needed to optimize the antimicrobial properties and reduce the likelihood of side effects.The nanostructures of self-assembled antimicrobial peptides offer new opportunities for antimicrobial therapy.They can act through a variety of mechanisms,including physical barrier effects,enhanced drug permeability,and as drug carriers.In addition,the multifunctionality of self-assembled antimicrobial peptides makes them ideally suited for the development of novel antimicrobial strategies,such as combining specific antimicrobial peptides to target a particular bacterial species or modifying the antimicrobial peptides to enhance their targeting of specific bacteria.The research and development of self-assembled antimicrobial peptides have brought new hope for combating drugresistant bacterial infections.This review provides a comprehensive and systematic overview of the design strategies employed to develop self-assembled nanomaterials with antimicrobial peptides and explores their applications in the treatment of bacterial infections.We discuss the design of self-assembled antimicrobial peptides based on amphiphilic amino acids(hydrophobic interactions,hydrogen bonding,electrostatic interactions,andπ-πstacking),as well as chemical modification strategies involving fatty acids(hydrophobic),polyethylene glycol(hydrophilic),and glycosylation(CH-π).Finally,recent advances in the use of peptide-based nanomaterials(e.g.,fibres,spheres,tubes,hydrogels,etc.)to create ordered nanostructures for the treatment of bacterial infections(e.g.,abdominal,skin,and lung infections)are presented,and their potential applications in other fields are outlined.It is hoped that this review will provide guidance for further research in this area and facilitate the development of novel bacteriostatic agents.