Antimicrobial peptides for bacterial infections and their biomedical applications

Due to the rapid development of multidrug-resistant (MDR) bacteria due to the inappropriate use and misuse of antibiotics and the ineffective performance of antibiotics against refractory biofilm-associated infections (BRI), there is an urgent need for novel alternative antimicrobials and strategies to combat bacterial infections. Antimicrobial peptides (AMPs) have attracted considerable interest due to their potent activity against MDR pathogens and biofilm-associated infections, coupled with a substantially reduced risk of driving antimicrobial resistance-especially when employed as alternatives or adjuncts to conventional antibiotics. With the development of nanocarrier-based delivery strategies, AMP nanomaterials significantly improve the therapeutic effect of AMP by improving the hydrolytic stability, in vivo half-life, solubility, and reducing cytotoxicity and hemolysis of AMP. Distinct from previous reviews that primarily focus on AMP sequence engineering or generic nanocarrier types, this work adopts a clinically oriented framework organized by infection site-including pulmonary, bloodstream, gastrointestinal, chronic wound, and implant-associated infections. Key therapeutic outcomes reported in the literature are systematically compared, such as reductions in minimum inhibitory concentration (MIC), biofilm eradication efficiency, survival benefits in sepsis models, and wound closure kinetics. Formulation design strategies, administration routes, and the rational application of nanocarriers constructed from metallic elements, biocompatible polymers, and lipid-based architectures are discussed in the context of specific infectious microenvironments. By correlating the physicochemical properties of nanocarriers-such as surface charge, degradation profile, and release kinetics-with therapeutic performance across diverse infection models, this review also addresses the current limitations of AMP-based formulations in clinical applications. Overall, this review provides insights into the advantages and disadvantages of AMP-based nanomaterials currently under development for the treatment of bacterial infections in the literature, bringing inspiration and recommendations for their future design.