A gallium-integrated nanoplatform for synergistic therapy of <i>Pseudomonas aeruginosa</i> wound infections

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 <i>P. aeruginosa</i> 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. <i>In vitro</i> assays demonstrated the superior antibacterial and antibiofilm efficacy of GaLPCN under light conditions, achieving 99.9% eradication of <i>P. aeruginosa</i> at low concentrations. Transcriptomic analysis revealed downregulation of key genes involved in oxidative stress responses, exopolysaccharide synthesis, and bacterial motility. <i>In vivo</i>, 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.