Inhibiting Osteolytic Breast Cancer Bone Metastasis by Bone-Targeted Nanoagent via Remodeling the Bone Tumor Microenvironment Combined with NIR-II Photothermal Therapy

文献类型： 外文期刊

第一作者： Zeng, Yaoxun

作者： Zeng, Yaoxun;Pan, Zhenxing;Yuan, Jiongpeng;Feng, Zhenzhen;Ye, Zhaoyi;Li, Yushan;Bao, Ying;Ran, Zhili;Li, Xinyi;Ye, Huiling;Zhang, Kun;Liu, Xujie;He, Yan;Song, Yuqiong;Chen, Zefeng

作者机构：

关键词： bone microenvironments; bone targeting; breast cancer bone metastasis; RNA-seq; synergistic therapies

期刊名称：SMALL （ 影响因子：13.3； 五年影响因子：13.2 ）

ISSN： 1613-6810

年卷期： 2023 年

页码：

收录情况： SCI

摘要： Bone is one of the prone metastatic sites of patients with advanced breast cancer. The "vicious cycle" 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-II photoresponsive bone-targeting nanosystems (CuP@PPy-ZOL NPs) are designed and synthesized. CuP@PPy-ZOL NPs can trigger the photothermal-enhanced Fenton response and photodynamic effect to enhance the photothermal treatment (PTT) effect and thus achieve synergistic anti-tumor effect. Meanwhile, they exhibit a photothermal enhanced ability to inhibit osteoclast differentiation and promote osteoblast differentiation, which reshaped the bone microenvironment. CuP@PPy-ZOL 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-ZOL NPs combined with PTT with NIR-II 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.

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