Functional Silver Nanoparticle as a Benign Antimicrobial Agent That Eradicates Antibiotic-Resistant Bacteria and Promotes Wound Healing

With the increased prevalence of antibiotic-resistant bacteria infections, there is a pressed need for innovative antimicrobial agent. Here, we report a benign ε-polylysine/silver nanoparticle nanocomposite (EPL-g-butyl@AgNPs) with polyvalent and synergistic antibacterial effects. EPL-g-butyl@AgNPs exhibited good stability in aqueous solution and effective antibacterial activity against both Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) bacteria without emergence of bacterial resistance. Importantly, the nanocomposites eradicated the antibiotic-resistant bacteria without toxicity to mammalian cells. Analysis of the antibacterial mechanism confirmed that the nanocomposites adhered to the bacterial surface, irreversibly disrupted the membrane structure of the bacteria, subsequently penetrated cells, and effectively inhibited protein activity, which ultimately led to bacteria apoptosis. Notably, the nanocomposites modulated the relative level of CD3⁺ T cells and CD68⁺ macrophages and effectively promoted infected wound healing in diabetic rats. This work improves our understanding of the antibacterial mechanism of AgNPs-based nanocomposites and offers guidance to activity prediction and rational design of effective antimicrobial nanoparticles.