Advances in peptide-based nanostrategies against drug-resistant bacteria: Natural amino acids to molecular modifications.

In recent years, self-assembled antimicrobial peptides (AMPs) have shown promise in biomedical applications due to their multifunctional properties and high therapeutic potential. This stable nanostructure significantly addresses the clinical limitations associated with peptides, such as protease degradation, limited in vivo efficacy, and short half-life during systemic or oral administration. In this review, we provide a comprehensive overview of the recent advancements in the innovative design of self-assembled nano AMPs and their therapeutic effects in vivo. We categorize design strategies for nanopeptides based on intermolecular forces between amino acids, including hydrophobic interactions, hydrogen bonding, π-π stacking, and cation-anion-π interactions. Additionally, we discuss novel chemical modifications, including hydrophobic modification of peptide chains, glycosylation, and amphiphilic polymerization. Finally, we explore the potential applications of nanopeptides in drug delivery. We hope to provide guidance on promising directions in the field, stimulate broad scientific interest and provide new, effective and selective solutions to the limitations of self-assembled AMPs in clinical applications.