Ge Jun, Yang Nailin, Yang Yuqi, Yu Hao, Yang Xiaoyuan, Wang Yingjie, Wang Tianyi, Cheng Shuning, Wang Yuanjie, Han Zhihui, Teng Yun, Zou Jun, Yang Huilin, Cheng Liang
Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu, China.
Bioact Mater. 2023 Jan 23;25:73-85. doi: 10.1016/j.bioactmat.2023.01.008. eCollection 2023 Jul.
Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.
骨肉瘤(OS)患者因其高度异质性和高转移率而预后较差。磁热疗(MHT)联合免疫疗法是治疗实体瘤和转移性肿瘤的有效策略。在此,我们将可生物降解的镁(Mg)宏观棒材与免疫疗法相结合,该棒材在低外部交变磁场下作为一种涡电流热磁剂,以实现对骨肉瘤的根治。镁棒(MgR)的涡电流热效应(ETE)显示出显著的细胞毒性作用,并增强了树突状细胞(DC)的成熟,温和的磁热疗诱导骨肉瘤细胞发生免疫原性细胞死亡(ICD)。联合免疫检查点阻断(ICB)疗法,我们对骨肉瘤取得了优异的治疗效果,进一步评估表明,MgR诱导的局部磁热疗增加了T细胞浸润和M1巨噬细胞的极化。有趣的是,可生物降解的MgR还促进了骨生成。我们的工作强调了可生物降解的MgR介导的不均匀ETE在骨肉瘤肿瘤微环境(TME)中诱导了全面的免疫激活,这将推动磁热疗在骨肉瘤有效治疗中的应用。