Platelet cell membrane-hybridized nanobubble for universal targeted and enhanced phototherapy against bacterial infections.

The rapid emergence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) underscores the urgent need for antibiotic-independent antibacterial strategies. Although phototherapy has emerged as a promising alternative, phototherapeutic agents often suffer from poor infection-site specificity, thereby risking collateral damage to healthy tissues and reducing the antibacterial efficacy. Here, we present a biomimetic, stimuli-responsive nanobubble platform, PSP@IR780-PFC(O2), which integrates broad-spectrum bacterial targeting with on-demand phototherapeutic activation triggered by bacterial pore-forming toxins (PFTs). Constructed by co-assembling oxygen-dissolved perfluorocarbon (PFC) with a hybrid membrane of phosphatidylcholine/sphingomyelin (PS) and platelet-derived membrane (PM), and loaded with the photosensitizer IR780, this nanobubble system exhibits robust binding affinity toward both Gram-positive and Gram-negative bacteria via platelet-specific surface adhesins. Moreover, the PS component confers a superior PFT-neutralizing capacity compared to native erythrocyte membranes, thereby enhancing the protection of host cells. Upon PFT-mediated membrane disruption, accelerated oxygen release from the PFC core amplifies local reactive oxygen species (ROS) generation under NIR irradiation, thereby enabling precise, enhanced, spatiotemporally controlled phototherapy. In vivo studies demonstrated effective accumulation at MRSA- and PA-infected sites, significant bacterial eradication, and rapid wound healing. Taken together, PSP@IR780-PFC(O2) offers a generalizable, pathogen-targeted, and toxin-responsive platform for enhanced antibacterial phototherapy, providing a compelling strategy to combat a broad range of bacterial infections without reliance on conventional antibiotics.