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This study presents an injectable pH\/ROS\u2010dual\u2010responsive hydrogel co\u2010loaded with enoblituzumab (B7\u2010H3 blocker) and Cl\u2010amidine (NETs suppressor). The hydrogel, formed by boronic ester bonds and Schiff base linkages, ensures precise drug release within the acidic, high\u2010ROS tumor microenvironment (TME). Notably, its localized intratumoral delivery avoids intravenous administration's systemic toxicity and off\u2010target effects, enabling high intratumoral accumulation with minimal systemic exposure. In orthotopic and subcutaneous OSCC models, intratumoral administration significantly suppressed tumor growth compared to monotherapies or controls. This enhanced antitumor effect arises from synergistic TME reprogramming: Cl\u2010amidine inhibits NETs formation to reduce barriers and facilitate robust CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration, while enoblituzumab, by targeting B7\u2010H3, restores cytotoxic T\u2010cell function and augments antibody\u2010dependent cellular cytotoxicity. Experimental evidence validates the suppression of OSCC invasion and metastasis through inhibition of B7\u2010H3 and NETs, which occurs by reversal of their induced epithelial\u2010mesenchymal transition (EMT). The hydrogel exhibits excellent biocompatibility without systemic toxicity. This TME\u2010responsive combination strategy offers a promising approach to enhance immunotherapy efficacy and overcome immune resistance in OSCC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202515431","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:43:52Z","timestamp":1770972232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["pH\/ROS\u2010Responsive Injectable Hydrogel Co\u2010Loaded with B7\u2010H3 Blocker and NETs Suppressor Boosts OSCC Synergistic Immunotherapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-3579","authenticated-orcid":false,"given":"Huan","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral and 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