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Metal ions play a critical role in modulating the innate immune response. However, the mechanisms by which metal ions facilitate dendritic cell maturation through the activation of interferon remain poorly understood. This research identifies a nanomaterial Calcium phosphate\u2010containing liposome (NanoCa), characterized by an atypical crystal structure and pH\u2010responsive profile. NanoCa promotes bone marrow\u2010derived dendritic cell maturation and exhibits antiviral effects and anti\u2010tumor properties in different tumor models. Also, NanoCa acts as an immunostimulant by fostering antibody production. Furthermore, when combined with programmed cell death 1 receptor (PD\u20101)\u00a0 blocking antibodies, NanoCa synergistically enhances anti\u2010tumor efficacy in CT26 models. Mechanistically, NanoCa rapidly releases Ca\n                    <jats:sup>2+<\/jats:sup>\n                    via the lysosome pathway post\u2010endocytosis, subsequently triggering interferon through the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010calcineurin (CaN) \u2010 nuclear factor of activated T cells 2 (NFATc2) \u2010 protein kinase C beta (PKC\u03b2) \u2010 interferon regulatory factor 3 (IRF3) signal pathway. Single\u2010cell RNA sequencing (scRNA\u2010seq) shows NanoCa increases the population of tumoral infiltrating dendritic cell (DC), C1qc+ TAM, and CD8T_eff cells and decreases the CD8T_ex and immunosuppressive SPP1+ TAM population in tumor\u2010draining lymph nodes. Overall, NanoCa shows translational potential for anti\u2010tumor immune therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/adma.202419870","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:24:45Z","timestamp":1751516685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Engineering a Lipid Nanoparticle with Atypical Calcium Crystal Structure for Enhanced IFN\u03b2\u2010Mediated Immunotherapy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8822-0770","authenticated-orcid":false,"given":"Yujie","family":"Luo","sequence":"first","affiliation":[{"name":"Institute of Systems Biomedicine Beijing Key Laboratory of Tumor Systems Biology NHC Key Laboratory of Medical Immunology Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Science Peking University Peking University Health Science Center Peking University  Beijing 100191 P. 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