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 ...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.展开更多
基金This article was partially supported by the National Natural Science Foundation of China(U20A20254,52072253,82172506,82030068)Collaborative Innovation Center of Suzhou Nano Science and Technology,the 111 Project,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,a Jiangsu Social Development Project(BE2019658)+1 种基金a Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20211544)Suzhou Key Laboratory of Nanotechnology and Biomedicine.L.Cheng was supported by the Tang Scholarship of Soochow University.
文摘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.
