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Crucially, LipoNCs@pGSDMB restore voltage-gated calcium channel (VGCC) expression in tumor cells, a prognostic biomarker identified through multiomics analysis of clinical specimens, thereby blocking calcium-dependent neurosignaling and disrupting prometastatic tumor-nerve cross-talk. In breast cancer bone metastasis models, this approach achieves 94% tumor suppression, complete pain resolution, and efficient bone restoration. By converging oxidation-responsive nanomaterial engineering, immunomodulation, and neural circuit reprogramming, this work establishes a paradigm-shifting neuroimmunotherapy platform that dismantles the self-reinforcing metastasis niche while addressing its debilitating sequelae.<\/jats:p>","DOI":"10.1126\/sciadv.ady1292","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:58:41Z","timestamp":1769194721000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Oxidation-activated nanotherapy boosts tumor immunity and disrupts tumor-nerve crosstalk to combat bone metastases and cancer pain"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9428-1853","authenticated-orcid":true,"given":"Zhaowei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of 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