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Multidrug-resistant bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) have become a major challenge in global public health. Given the decreasing efficacy of traditional antibiotic treatments, the development of non-antibiotic antibacterial strategies is urgently needed. Phototherapy, as an emerging alternative, shows promising application prospects, but the existing photosensitizers often lack targeting ability to the infection site and can easily cause damage to normal tissues, limiting their efficacy. Recently, the research team led by Professor Chen Yijie from the Second Affiliated Hospital of Wenzhou Medical University published a research paper titled "Platelet cell membrane-hybridized nanobubble for universal targeted and enhanced phototherapy against bacterial infections" in the Journal of Controlled Release (CSCD, Zone 1, IF = 11.5). The team combined the broad-spectrum bacterial targeting strategy with on-demand phototherapy triggered by bacterial pore-forming toxins (PFTs) (TROP) and successfully constructed a biomimetic, toxin-responsive nanobubble platform - PSP@IR780-PFC(O₂). This platform is composed of a phosphatidylcholine/sphingomyelin (PS) and platelet-derived membrane (PM) co-assembled hetero-membrane loaded with the photosensitizer IR780, and encapsulates the perfluorocarbon (PFC) core with dissolved oxygen. By leveraging the unique surface adhesion factors of platelet membranes, the nanobubbles can achieve broad-spectrum targeting of Gram-positive and Gram-negative bacteria. Notably, compared to traditional red blood cell membranes, the PS component endows this system with stronger PFTs neutralization ability, which can significantly enhance the protective effect on host cells. Under the membrane pore-forming action mediated by bacterial PFTs, the oxygen in the PFC core is accelerated to release, and in the near-infrared light, the generation of local reactive oxygen species (ROS) is enhanced, thereby achieving precise, enhanced, and spatiotemporally controllable phototherapy antibacterial effects. In vivo studies further confirmed that this platform can efficiently accumulate at the infection sites of MRSA and Pseudomonas aeruginosa PA, significantly clear the bacterial load under near-infrared light, and promote the rapid healing of infected wounds. In summary, the PSP@IR780-PFC(O₂) platform constructed in this study integrates pathogen targeting, toxin response, and enhanced phototherapy, providing a highly promising universal strategy for combating multidrug-resistant bacterial infections.
