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

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 drug- resistant 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, and it-it stacking), as well as chemical modification strategies involving fatty acids (hydrophobic), polyethylene glycol (hydrophilic), and glycosylation (CH-it). 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.