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Here, we report a paradigm\u2010shifting bidirectional Ca\n                    <jats:sup>2+<\/jats:sup>\n                    redistribution nanomodulator (RP@AA\u2010Lip) that rewires Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis across intracellular\u2010extracellular compartments to orchestrate a self\u2010reinforcing mechanical\u2010immunological cascade for deep photothermal\u2010immunotherapy (PTI). This core\u2010shell nanomodulator RP@AA\u2010Lip consists of hypoxia\u2010targeting Rhodopseudomonas palustris (RP) as the photothermal core and an ascorbic acid (AA)\u2010enriched liposome (Lip) shell. Under NIR irradiation, RP activates TRPV1\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx, while AA inhibits PMCA4\u2010driven Ca\n                    <jats:sup>2+<\/jats:sup>\n                    efflux, jointly triggering intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload to induce mitochondrial damage and thermoresistance reversal for amplified immunogenic cell death. We find that extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    depletion disassembles E\u2010cadherin junctions and softens tumor stiffness 4.23\u2010fold, enabling deep tumor penetration (up to 500\u00a0\u00b5m) and robust cytotoxic T cell (CTL) infiltration. Concurrently, the intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload further stiffens tumor cells to establish mechanical immunosurveillance that improves CTL\u2010mediated tumor killing. In triple\u2010negative breast cancer models, this integrated strategy elicits a robust antitumor immune cascade to remodel the tumor microenvironment and suppress tumor progression. Collectively, this work pioneers a compartmental Ca\n                    <jats:sup>2+<\/jats:sup>\n                    engineering strategy that unites nanomaterial design, ion signaling, and mechanical immunology, offering a transformative and translatable blueprint for deep PTI against stroma\u2010rich solid tumors.\n                  <\/jats:p>","DOI":"10.1002\/advs.77625","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:43:46Z","timestamp":1788929026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Mechanical Remodeling via Bidirectional Calcium Redistribution Enables Deep Photothermal\u2010Immunotherapy"],"prefix":"10.1002","author":[{"given":"Hongjuan","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou China"},{"name":"Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment 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