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In this study, we construct IROTD nanoparticles (IROTD NPs) through self\u2010assembly of a norcantharidin (NCTD)\u2010OXA\u2010conjugated polymer (P2) and the near\u2010infrared (NIR) photosensitizer DTIR780. Under 808\u00a0nm laser irradiation, IROTD NPs generate heat and reactive oxygen species (ROS) while release OXA and NCTD, result in severe DNA damage and potent induction of ICD within tumor cells. Concurrently, NCTD inhibits DNA repair mechanisms and down\u2010regulates PD\u2010L1expression, thereby increase the infiltration of cytotoxic T\u2010cell and amplify systemic antitumor immunity. Leverage the enhanced permeability and retention (EPR) effect, IROTD NPs efficiently accumulate at tumor sites, result in remarkable inhibition of tumor growth and recruitment of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes, which collectively contribute to the activation of a systemic antitumor immunity. In a bilateral tumor model, IROTD NPs effectively inhibit both primary and distant tumor growth. Overall, this work presents a rationally designed combinatorial nanoplatform that effectively ignites systemic immune response, thus establish a prospective chemo\u2010immunotherapeutic stratagem for cancer treatment.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505173","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T10:48:31Z","timestamp":1771584511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oxaliplatin\/Norcantharidin Prodrug Co\u2010Loaded Nanoparticles: Synergistic DNA\u2010Repair Blockade Plus PD\u2010L1 Downregulation for Inhibit Tumor Growth and Metastasis"],"prefix":"10.1002","volume":"15","author":[{"given":"Peng\u2010Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Henan Key Laboratory of Natural Medicine Innovation and Transformation Henan University  China"},{"name":"State Key Laboratory of Antiviral Drugs Henan University  Kaifeng 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