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The biofilm environment induces excessive interleukin-10 (IL-10) production in dendritic cells, leading to inhibition of the cGAS\u2013STING signaling pathway and T-cell activation. Therefore, strategies that simultaneously disrupt biofilm structure and reverse the immunosuppressive microenvironment are urgently needed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We developed a near-infrared\u2013responsive MnO\u2082@PMS nanoregulator that integrates photothermal catalysis with metabolic immunotherapy. Upon laser irradiation, MnO\u2082@PMS generated oxygen-independent sulfate radicals (\u2022SO\u2084\u207b) that efficiently degraded the biofilm matrix and suppressed bacterial glutamate metabolism, thereby reducing the synthesis of poly-\u03b3-glutamic acid. This metabolic inhibition decreased biofilm-derived glutamate accumulation and downregulated IL-10 production in dendritic cells, leading to reactivation of the cGAS\u2013STING pathway and restoration of antigen presentation. In vivo, MnO\u2082@PMS treatment promoted mature dendritic-cell and T-cell activation, reduced bacterial burden, alleviated local inflammation, and enhanced angiogenesis and tissue repair, while exhibiting favourable short-term biocompatibility in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study introduces a glutamate-targeted nanoplatform that couples biofilm destruction with immune reprogramming in a chronic biofilm infection model. By bridging metabolic regulation and immune activation, MnO\u2082@PMS complements existing nanozyme and photothermal antibiofilm strategies by illustrating a mechanistically supported approach that integrates oxygen-independent sulfate radical catalysis with modulation of glutamate\u2013IL-10\u2013associated immunosuppression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-025-04016-3","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T02:26:49Z","timestamp":1770172009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glutamate nanoregulator for metabolic immunotherapy of biofilm-associated implant infections"],"prefix":"10.1186","volume":"24","author":[{"given":"Heng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geyong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-3815","authenticated-orcid":false,"given":"Pei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"4016_CR1","doi-asserted-by":"publisher","first-page":"1028560","DOI":"10.3389\/fmicb.2022.1028560","volume":"13","author":"SB Behbahani","year":"2022","unstructured":"Behbahani SB, Kiridena SD, Wijayaratna UN, Taylor C, Anker JN, Tzeng TJ. pH variation in medical implant biofilms: Causes, measurements, and its implications for antibiotic resistance. 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