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Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion\u2010responsive and calcium peroxide\u2010based nanoparticles carrying the bone\u2010targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O<jats:sub>2<\/jats:sub>, while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor\u2010bearing legs with an 808\u00a0nm laser source, the O<jats:sub>2<\/jats:sub> and free photosensitizer produced <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub> by the reaction of the nanoparticles with phosphate ions, further boosting the anti\u2010tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis.<\/jats:p>","DOI":"10.1002\/adhm.202402216","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T09:32:26Z","timestamp":1723023146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phosphate Ion\u2010Responsive and Calcium Peroxide\u2010Based Nanomedicine for Bone\u2010Targeted Treatment of Breast Cancer Bone Metastasis"],"prefix":"10.1002","volume":"13","author":[{"given":"Dehui","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory of New Pharmaceutical Preparations and Excipients Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education Key Laboratory of Chemical Biology of Hebei Province College of Chemistry and Material Science Hebei University  Baoding 071002 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