A gallium-integrated nanoplatform for synergistic therapy of Pseudomonas aeruginosa wound infections

Abstract

With the growing threat of antimicrobial resistance, novel antibacterial strategies are required for the treatment of bacterial infections. Herein, we constructed a gallium-integrated metal–organic framework nanoplatform (denoted as GaLPCN) to achieve synergistic photodynamic and iron-interference therapy of P. aeruginosa infections. GaLPCN consists of a porphyrin-based MOF core functionalized with cationic poly(L-lysine) and loaded with gallium ions. The modified surface enhances bacterial membrane binding and biofilm penetration, while gallium disrupts iron-dependent metabolic pathways. Under light irradiation, GaLPCN generates substantial reactive oxygen species (ROS), leading to bacterial membrane damage and oxidative stress. In vitro assays demonstrated the superior antibacterial and antibiofilm efficacy of GaLPCN under light conditions, achieving 99.9% eradication of P. aeruginosa at low concentrations. Transcriptomic analysis revealed downregulation of key genes involved in oxidative stress responses, exopolysaccharide synthesis, and bacterial motility. In vivo, GaLPCN plus light treatment significantly accelerated wound healing in a murine infection model, reduced bacterial burden, promoted collagen deposition, and suppressed inflammatory responses. This multifunctional nanoplatform represents a promising non-antibiotic strategy for combating resistant bacterial infections.