Site‐Specific Antibacterial Strategy for Multi‐Pathway Treatment of Drug‐Resistant Skin Infections

Abstract Drug‐resistant skin infections, especially those caused by multidrug‐resistant (MDR) bacteria, remain a major public health concern due to the limited efficacy of conventional antibiotics and biofilm‐associated tolerance. Herein, a site‐specific antibacterial strategy based on a multi‐pathway microneedle (MN) patch system is presented for effective treatment of methicillin‐resistant Staphylococcus aureus (MRSA)‐infected wounds and abscesses. The MN patch co‐delivers vancomycin and photoactive black phosphorus quantum dots (BPQDs) encapsulated in macrophage membrane‐coated cationic liposomes, thereby integrating antibiotic therapy with phototherapy. Upon light activation, BPQDs generate localized hyperthermia and reactive oxygen species, which synergize with vancomycin to eradicate bacteria and reduce the risk of resistance development. The dissolvable MN array ensures efficient penetration through the skin barrier, enabling targeted and sustained release at the infection site. In vivo, this multi‐pathway intervention significantly accelerates wound closure, reduces abscess size, suppresses inflammation, and promotes tissue regeneration by remodeling the infectious microenvironment. Overall, this work demonstrates a promising localized therapeutic platform that harnesses multi‐pathway antibacterial mechanisms to combat MDR bacteria and facilitate the healing of drug‐resistant skin infections.