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While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off\u2010target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore\u2010forming toxins trigger on\u2010demand payload release. Upon subsequent near\u2010infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on\u2010demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high\u2010priority pathogens.<\/jats:p>","DOI":"10.1002\/smll.202203292","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T06:05:45Z","timestamp":1658383545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Toxin\u2010Enabled \u201cOn\u2010Demand\u201d Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin\u2010Resistant <i>Staphylococcus aureus<\/i> Infection"],"prefix":"10.1002","volume":"18","author":[{"given":"Deli","family":"Zhuge","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology the Second Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang 325027 China"},{"name":"Department of Pharmaceutics School of Pharmaceutical Sciences of Wenzhou Medical 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