Probiotics-Armed Cationic Photosensitizer for Combating Chronic Wound Infections with Multidrug-Resistant Bacteria Through Dismantling Biofilms and Reprogramming Hostile Wound Milieu.

Chronic wound infections caused by multidrug-resistant (MDR) bacteria present a serious global health challenge. Clinical treatment outcomes are significantly impeded by two critical pathological barriers: stubborn bacterial biofilms that block antimicrobial penetration, and a highly oxidative, inflammatory microenvironment that hinders tissue regeneration. To overcome these challenges, we developed a novel integrated therapeutic platform to concurrently dismantle biofilms and reprogram the hostile wound milieu, thereby enabling synergistic healing of chronic wound. This platform, LGG@TBTCP-BOH, consists of the probiotic Lactobacillus rhamnosus GG (LGG) surface-conjugated with a lipophilic cationic photosensitizer (PS, TBTCP-BOH) via stimuli-responsive borate ester linkages. The platform selectively dissociates in response to the acidic conditions of chronic wounds. Upon release, LGG actively metabolizes biofilm matrix saccharides, degrading extracellular polymeric substances (EPS) to promote deep penetration of the PS, which, upon photoactivation, efficiently eradicates embedded bacteria deep inside the biofilm. Subsequently, the probiotic further modulates the wound microenvironment by scavenging excess reactive oxygen species (ROS), resolving persistent inflammation, and stimulating angiogenesis, which collectively accelerate tissue repair. This work presents an innovative probiotic-photodynamic therapy (PDT) strategy, which offers valuable insights for the design of intelligent antibacterial platforms against persistent infections and establishes a promising therapeutic paradigm for the treatment of chronic, biofilm-associated wounds.