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Here, a programmable calcification nanoplatform (CaIM) is developed using in situ growth of calcium peroxide (CaO\n                    <jats:sub>2<\/jats:sub>\n                    ) on black phosphorus (BP) nanosheets, followed by hyaluronic acid encapsulation. Unlike conventional physical adsorption or co\u2010precipitation, this in situ growth strategy yields crystalline CaO\n                    <jats:sub>2<\/jats:sub>\n                    uniformly anchored on the BP matrix, enabling synchronized release of Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , phosphate, and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    in the tumor microenvironment. CaIM induces potent intracellular calcium overload and oxidative stress, triggering mitochondrial dysfunction, cell death, and extensive biological calcification readily visualized via computed tomography (CT). Multi\u2010omics profiling identifies the mucolipin channel MCOLN2 as a key mediator regulating calcium flux, facilitating stable active biomineralization rather than passive necrotic calcification. This active calcification, coupled with mitochondrial damage, effectively reshapes the immunosuppressive microenvironment by promoting macrophage polarization and T cell infiltration. These findings establish a calcium signaling\u2010driven paradigm integrating nanocomposite design with synergistic calcium stress, oxidative damage, and immune activation, offering a robust foundation for calcification\u2010based cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.76642","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:49:19Z","timestamp":1784548159000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Programmable Calcification Nanoplatform for Loco\u2010Regional Calcification\u2010Immune Hepatocellular Carcinoma Therapy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3473-2248","authenticated-orcid":false,"given":"Long","family":"Liu","sequence":"first","affiliation":[{"name":"Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"National Local Joint Engineering Research Center for Precision Surgery &amp; Regenerative Medicine The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Regenerative and Reconstructive Medicine Med\u2010X Institute The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Biology School of Life Sciences Xiamen University  Xiamen 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