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一种通过硼硅酸盐生物活性玻璃增强适度磁热疗来促进肿瘤性骨再生的策略。

A strategy for challenging tumorous bone regeneration by borosilicate bioactive glass boosting moderate magnetic hyperthermia.

作者信息

Fan Mengke, Liu Chunyu, Zhang Yueyao, Zhang Jinlei, Lu Yang, Su Kun, Tian Pengfei, Zhou Yabin, Zhang Liyan, Gao Xianda, Li Honglong, Li Shuaijie, Du Ping, Li Xian, Chen Wei, Cui Xu, Pan Haobo

机构信息

Shenzhen Key Laboratory of Marine Biomedical Materials, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Department of Orthopaedic Surgery, The Hebei Medical University Third Hospital, Shijiazhuang, China.

出版信息

Nat Commun. 2025 Aug 28;16(1):8057. doi: 10.1038/s41467-025-63270-z.

Abstract

Osteosarcoma (OS), with a high tendency for recurrence and metastasis, is associated with severe impairment of bone regeneration. The inherent temperature-sensitive property of tumors positions magnetic hyperthermia (MH) as an increasingly significant area in non-pharmacological cancer treatments. However, the temperature threshold for tumor ablation often causes tissue damage and bone homeostasis imbalance. Therefore, development of moderate MH for OS, capable of achieving tumor ablation while concurrently restoring bone homeostasis, offers significant potential for addressing this challenge. This study integrates magnetothermal nanoparticles with defined temperature thresholds and borosilicate bioactive glass (BSG) to create an injectable magnetothermal bioactive system that allows for regulation of MH temperature. The ionic and alkaline microenvironment from BSG degradation primarily impairs the malignant behavior of OS cells by activating the TNF signaling pathway. This sickening effect diminishes the hyperthermia tolerance of OS cells, thereby boosting apoptosis of OS cells, even in the presence of the limited anti-tumor effects of moderate MH. Furthermore, the combination of moderate MH and BSG also promotes optimal bone formation by stimulating human bone marrow mesenchymal stem cells (hBMSCs) via calcium and JAK-STAT3 signaling pathways. Collectively, this flourishes the therapeutic approaches and theories for the prevention and management of clinically refractory bone tumors.

摘要

骨肉瘤(OS)具有较高的复发和转移倾向,与骨再生的严重受损有关。肿瘤固有的温度敏感性使磁热疗(MH)成为非药物癌症治疗中一个日益重要的领域。然而,肿瘤消融的温度阈值常常会导致组织损伤和骨稳态失衡。因此,开发适用于骨肉瘤的适度磁热疗,能够在实现肿瘤消融的同时恢复骨稳态,为应对这一挑战提供了巨大潜力。本研究将具有确定温度阈值的磁热纳米颗粒与硼硅酸盐生物活性玻璃(BSG)相结合,创建了一种可注射的磁热生物活性系统,该系统能够调节磁热疗温度。BSG降解产生的离子和碱性微环境主要通过激活TNF信号通路来损害OS细胞的恶性行为。这种有害作用降低了OS细胞的热耐受性,从而促进OS细胞凋亡,即使在适度磁热疗的抗肿瘤作用有限的情况下也是如此。此外,适度磁热疗与BSG的联合还通过钙和JAK-STAT3信号通路刺激人骨髓间充质干细胞(hBMSCs),从而促进最佳的骨形成。总的来说,这丰富了临床上难治性骨肿瘤预防和管理的治疗方法和理论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0512/12394710/324b5d713c70/41467_2025_63270_Fig1_HTML.jpg

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