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To address these challenges, PEI\/siENPP1@Mn\u2010ZIF\u20108 (PEMZ) is reported, an integrated gene\u2013chemodynamic\u2013immune nanocomplex that activates the cyclic GMP\u2010AMP synthase\u2010stimulator of interferon genes (cGAS\u2010STING) pathway through a previously unattainable triple\u2010activation mechanism. PEMZ efficiently encapsulates siENPP1, protects it from degradation, and enables acid\u2010responsive cytosolic release, resulting in sustained\n                    <jats:italic>ectonucleotide pyrophosphatase\/phosphodiesterase 1<\/jats:italic>\n                    (\n                    <jats:italic>ENPP1<\/jats:italic>\n                    ) silencing and accumulation of tumor\u2010derived cyclic 2\u2032,3\u2032\u2010GMP\u2010AMP (cGAMP). Simultaneously, the Mn\n                    <jats:sup>2+<\/jats:sup>\n                    \/Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ions released from the trienzyme\u2010mimetic nanocomplex, which exhibits peroxidase\u2010, catalase\u2010, and glutathione peroxidase\u2010like activities, amplify intracellular reactive oxygen species, deplete glutathione, and trigger mitochondrial dysfunction. This coordinated redox disruption induces immunogenic cell death and further enhances STING signaling. In vitro and in vivo studies demonstrate that PEMZ markedly suppresses TNBC proliferation and metastasis, promotes dendritic cell maturation, and increases intratumoral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration, achieving potent tumor inhibition with minimal systemic toxicity. This work establishes PEMZ as a mechanistically integrated nano\u2010immunotherapy platform, offering a promising and broadly applicable strategy for the precision treatment of TNBC and other ENPP1\u2010overexpressing cancers.\n                  <\/jats:p>","DOI":"10.1002\/adma.73878","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T03:55:26Z","timestamp":1782446126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An siENPP1\u2010Delivering Bimetallic MOF Nanocomplex Enables Triple Activation of the cGAS\u2010STING Pathway for Synergistic Triple\u2010Negative Breast Cancer Therapy"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9920-0247","authenticated-orcid":false,"given":"Shi","family":"Chen","sequence":"first","affiliation":[{"name":"College of Laboratory Medicine Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education) Chongqing Medical University  Chongqing P. 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