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However, activation of the cGAS\u2013STING pathway alone is seldom sufficient to eliminate established tumors. Here, we report the engineering of zinc\/manganese (Zn\/Mn)\u2010based metal\u2013organic framework (MOF) nanoparticles, that is, AMP@Zn\/Mn\u2010MOF, comprising Zn\/Mn\u2010MOF nanoparticles as the carrier and the STING agonist c\u2010di\u2010AMP diammonium as the therapeutic drug for reinforcing antitumor immune responses. These therapeutic nanoplatforms can significantly activate the cGAS\u2012STING pathway and facilitate the innate immune response. Furthermore, the peroxidase (POD)\u2010mimetic and glutathione oxidase (GSHox)\u2010mimetic activities of AMP@Zn\/Mn\u2010MOF can significantly potentiate tumor cell death and effectively induce robust immunogenic cell death (ICD), thereby amplifying the cGAS\u2013STING pathway. Moreover, AMP@Zn\/Mn\u2010MOF reprogrammed the immunosuppressive tumor microenvironment by promoting intratumoral lymphocyte infiltration, thereby significantly suppressing the growth of murine MC38 tumors in mice. Notably, AMP@Zn\/Mn\u2010MOF amplified the therapeutic effect of anti\u2010programmed death ligand 1 (\u03b1PD\u2010L1) blockade by triggering systemic antitumor responses, resulting in a notable abscopal effect to effectively inhibit distant tumors. In summary, AMP@Zn\/Mn\u2010MOF offers a nanoplatform with enhanced antitumor effectiveness through activation of the cGAS\u2013STING pathway and ICD, suggesting that enhanced immune checkpoint blockade\u2010based immunotherapy is promising for colon cancer treatment.<\/jats:p>","DOI":"10.1002\/advs.202521146","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:47:26Z","timestamp":1769593646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic Activation of Immunogenic Cell Death and the cGAS\u2013STING Pathway by Engineered Zinc\/Manganese\u2010Based Metal\u2013Organic Framework Nanoplatforms for Colon Cancer Immunotherapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Bingzi","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Colorectal and Anal Surgery, Zhejiang\u2013Finland Joint Laboratory of Gastrointestinal Tumor Metabolism and 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