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Clinical practices highly rely on mechanical debridement and antibiotics, which often fail and lead to persistent and recurrent infections. The main culprits are 1) persistent bacteria reviving, colonizing, and rejuvenating biofilms, and 2) secondary pathogen exposure, particularly in individuals with chronic diseases. Addressing how to inhibit persistent bacteria revival and prevent reinfection simultaneously is still a major challenge. Herein, an oligo\u2010ethylene glycol\u2010modified lipophilic cationic photosensitizer (PS), TBTCP\u2010PEG7, is developed. It effectively eradicates Methicillin\u2010Resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) under light irradiation. Furthermore, TBTCP\u2010PEG7\u2010mediated photodynamic therapy (PDT) not only conquers stubborn biofilm infections by downregulating the two\u2010component system (TCS), quorum sensing (QS), and virulence factors, thereby reducing intercellular communication, inhibiting persistent bacterial regrowth and biofilm remodeling but also prevents reinfection by upregulating heat shock protein\u2010related genes to induce immunogenetic cell death (ICD) and establish immune memory. In vivo, TBTCP\u2010PEG7 efficiently eradicates MRSA biofilm adhered to medical catheters, stimulates angiogenesis, reduces inflammatory factor expression, and accelerates wound healing. Furthermore, ICD promotes short\u2010term immune and long\u2010term immunological memory for coping with secondary infections. This two\u2010pronged strategy not only effectively overcomes stubborn, persistent and recurrent biofilm infection, but also provides theoretical guidance for designing the next generation of antibacterial materials.\n                  <\/jats:p>","DOI":"10.1002\/adma.202411468","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T07:41:08Z","timestamp":1735198868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Photoimmunologic Therapy of Stubborn Biofilm via Inhibiting Bacteria Revival and Preventing Reinfection"],"prefix":"10.1002","volume":"37","author":[{"given":"Jia\u2010Li","family":"Wang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Sichuan University  Chengdu 610065 China"},{"name":"Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 P. 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