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The \u201cvicious cycle\u201d between osteoclasts and breast cancer cells plays an essential role in osteolytic bone metastasis from breast cancer. In order to inhibit bone metastasis from breast cancer, NIR\u2010II photoresponsive bone\u2010targeting nanosystems (CuP@PPy\u2010ZOL NPs) are designed and synthesized. CuP@PPy\u2010ZOL NPs can trigger the photothermal\u2010enhanced Fenton response and photodynamic effect to enhance the photothermal treatment (PTT) effect and thus achieve synergistic anti\u2010tumor effect. Meanwhile, they exhibit a photothermal enhanced ability to inhibit osteoclast differentiation and promote osteoblast differentiation, which reshaped the bone microenvironment. CuP@PPy\u2010ZOL NPs effectively inhibited the proliferation of tumor cells and bone resorption in the in vitro 3D bone metastases model of breast cancer. In a mouse model of breast cancer bone metastasis, CuP@PPy\u2010ZOL NPs combined with PTT with NIR\u2010II significantly inhibited the tumor growth of breast cancer bone metastases and osteolysis while promoting bone repair to achieve the reversal of osteolytic breast cancer bone metastases. Furthermore, the potential biological mechanisms of synergistic treatment are identified by conditioned culture experiments and mRNA transcriptome analysis. The design of this nanosystem provides a promising strategy for treating osteolytic bone metastases.<\/jats:p>","DOI":"10.1002\/smll.202301003","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T04:45:50Z","timestamp":1684730750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Inhibiting Osteolytic Breast Cancer Bone Metastasis by Bone\u2010Targeted Nanoagent via Remodeling the Bone Tumor Microenvironment Combined with NIR\u2010II Photothermal Therapy"],"prefix":"10.1002","volume":"19","author":[{"given":"Yaoxun","family":"Zeng","sequence":"first","affiliation":[{"name":"Allan H. Conney Laboratory for Anticancer Research School of Biomedical and Pharmaceutical Sciences Guangdong University of Technology  Guangzhou Guangdong 510006 P. R. 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