Fan Dehui, Li Jing, Li Luwei, An Ming, Yang Hua, Zhou Guoqiang, Gao Shutao, Bottini Massimo, Zhang Jinchao, Ge Kun
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, China.
Orthopedics Department, Bao Ding NO.1 Central Hospital, Baoding, 071000, China.
Adv Healthc Mater. 2024 Dec;13(31):e2402216. doi: 10.1002/adhm.202402216. Epub 2024 Aug 7.
The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion-responsive and calcium peroxide-based nanoparticles carrying the bone-targeting 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, while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor-bearing legs with an 808 nm laser source, the O and free photosensitizer produced O by the reaction of the nanoparticles with phosphate ions, further boosting the anti-tumor 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.
乳腺癌骨转移的治疗是一项尚未解决的临床挑战，主要是因为目前的治疗方法无法同时阻断肿瘤生长和修复转移部位的溶骨性骨损伤。在此，该研究开发了一种新型纳米药物来治疗乳腺癌骨转移。这种纳米药物基于磷酸根离子响应性且以过氧化钙为基础的纳米颗粒，其表面携带骨靶向剂唑来膦酸，并负载有光敏剂吲哚菁绿。在对乳腺癌骨转移小鼠模型进行静脉给药后，纳米颗粒有效地在骨转移部位聚集，与游离磷酸根离子反应，形成羟基磷灰石纳米聚集体并产生氧气，同时释放光敏剂。羟基磷灰石纳米聚集体引发胶原骨基质的再矿化并触发肿瘤细胞凋亡。在用808nm激光源照射荷瘤腿部时，纳米颗粒与磷酸根离子反应产生的氧气和游离光敏剂产生单线态氧，进一步增强抗肿瘤效果。肿瘤杀伤阻碍了骨转移部位的恶性循环，从而实现溶骨阻断并进一步促进骨基质的再矿化。这项工作为开发一种治疗乳腺癌骨转移的新型、安全且有效的方法提供了思路。
