NIR-activated antimicrobial peptide-functionalized nanoparticles for eradication of biofilms and healing of infected...

The formation of bacterial biofilms at infection sites represents a major obstacle to the effective healing of diabetic wounds. Biofilm-associated diabetic wounds are exceedingly difficult to manage, compounded by the increasing prevalence of antibiotic-resistant strains and the limited pipeline of novel antibacterial agents. To address this challenge, we designed polydopamine-HHC36-indocyanine green nanoparticles (PHI NPs) as an alternative therapeutic platform to conventional antibiotics. PHI NPs were fabricated by encapsulating the phototherapeutic agent indocyanine green (ICG) within a polydopamine (PDA) matrix, followed by surface functionalization with the cationic antimicrobial peptide HHC36 for autonomous and selective pathogen targeting. In vitro, PHI NPs bound Staphylococcus aureus with high affinity. Following intravenous administration in vivo, PHI NPs effectively accumulated at infected sites in a murine diabetic wound model. Upon near-infrared (NIR) laser irradiation, PHI NPs disrupted the biofilm architecture and subsequently eradicated the exposed bacteria through synergy between phototherapy (combining photothermal and photodynamic effects) and the antimicrobial peptide. Notably, bactericidal efficacy was robust under mild photothermal conditions (<45 °C), ensuring a favorable safety profile. In conclusion, PHI NPs constitute a potent and biocompatible platform for eradicating biofilm-associated infections and promoting wound healing of diabetic wounds whilst avoiding induction of antibiotic resistance.