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Here, we report a pH\u2010responsive, surface charge\u2010adaptive multifunctional nanosystem (DA\u2010L@DTTB\/Bro) for efficient in\u00a0vivo treatment of biofilm\u2010associated infections. The nanosystem integrates pH\u2010triggered charge adaptation, in situ self\u2010aggregation, photothermal responsiveness, enzymatic EPS degradation, and NIR\u2010II imaging. Cationic phospholipid AGPDP, together with cholesterol and thermosensitive DPPC, self\u2010assembled into liposomes encapsulating bromelain in the hydrophilic core and an NIR\u2010II\u2010emissive photothermal agent (DTTB) in the hydrophobic layer. Surface modification with DA\u2010functionalized chitosan (CS\u2010DA) generates negatively charged nanoparticles for prolonged circulation. At acidic infection sites, DA hydrolysis restores the cationic surface, enhancing biofilm penetration, while residual CS\u2010DA induces self\u2010aggregation to improve retention. NIR irradiation triggers DTTB\u2010mediated hyperthermia, directly killing bacteria and disassembling liposomes to release bromelain, which degrades EPSs and facilitates biofilm dispersion. The nanosystem eradicates methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    biofilms in vitro with 99.99% efficiency, enables high\u2010contrast NIR\u2010II imaging, persists at abscess sites in vivo, and accelerates wound healing. Furthermore, it demonstrates effective therapeutic activity against biofilm\u2010associated infections in deep pulmonary tissues. This study presents a versatile intravenous strategy for targeted, synergistic therapy against biofilm\u2010associated infections in vivo.\n                  <\/jats:p>","DOI":"10.1002\/adma.73749","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:40:43Z","timestamp":1781847643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acid\u2010Triggered, Enzyme\u2010Enabled EPS\u2010Degrading Nanoplatform With Enhanced In Situ Retention for Intravenous Biofilm Therapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Bo","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Functional Polymer Materials of Ministry of Education State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center For New Organic Matter, College of Chemistry Nankai University  Tianjin 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