NIR-responsive carbon monoxide nanoplatform for synergistic antibacterial and anti-inflammatory therapy of refractory keratitis and biofilm-infected wounds

Drug-resistant bacterial biofilms hinder the treatment of persistent infections by limiting drug penetration and reducing bacterial susceptibility through their dense extracellular matrix and active signaling networks. Herein, we developed a near-infrared (NIR) light-responsive, bacteria-targeting nanoplatform, termed UCMSP-CL, for localized carbon monoxide (CO) delivery and biofilm eradication. UCMSP-CL disrupts biofilm architecture and adheres to bacteria through electrostatic interactions and enzyme-substrate recognition. Subsequent NIR irradiation triggers local CO release, which induces severe bacterial metabolic exhaustion by inhibiting the bacterial respiratory chain, depleting ATP and compromising membrane integrity, while exerting potent anti-inflammatory effects. In murine models of methicillin-resistant Staphylococcus aureus (MRSA) keratitis and infected skin wounds, NIR-irradiated UCMSP-CL markedly reduced bacterial burden, promoted biofilm clearance, alleviated local inflammation, and accelerated tissue repair. These findings establish a controllable platform that couples antibacterial and anti-inflammatory activities, offering a potential strategy for treating biofilm-associated and drug-resistant infections.