Epsilon-polylysine microneedle potentiating MXene-mediated photothermal ablation for combating antibiotic-resistant bacterial infections

Antimicrobial peptides show promise in enhancing photothermal therapy, but their application is often limited by the challenge of constructing a delivery system that balances efficacy and safety. Our research demonstrated that the bactericidal efficacy of V₂C MXene-mediated photothermal therapy is enhanced in a concentration-dependent relationship with the introduction and coating of the antimicrobial peptide ε-polylysine (EPL). EPL exhibited a dual role in enhancing bacterial binding and disrupting bacterial membranes, thereby increasing heat transfer efficiency and reducing bacterial resistance to photothermal ablation. The core strategy of this study was to exploit the combined membranolytic-photothermal effect of EPL and V₂C by extensively applying EPL while regulating V₂C nanosheets usage to prevent overheating. This approach aims to achieve potent bactericidal efficacy through photothermal therapy below 60 °C. Consequently, we developed dissolving microneedles incorporated with V₂C nanosheets, where EPL served as the antimicrobial agent and primary matrix, increasing its loading capacity and minimizing the need for inactive excipients. Notably, this microneedle achieved a 99.9 % reduction in the abundance of methicillin-resistant Staphylococcus aureus on infected skin after a single application and resulted in a 92-fold reduction in the bacterial load compared to the group treated with commercial Bactroban ointment, with no apparent toxicity to the mice.