Thermo-Responsive Polypeptide Hydrogels Locally Deliver Immunomodulators Combined With Radiotherapy For Synergistic Treatment Of Spinal Metastases Of Breast Cancer

Objective: Combining radiotherapy and immunotherapy to induce immunogenic death of mouse tumor cells through radiotherapy,and synergistically with the immunomodulator carried by the hydrogel,to achieve the regulation of the tumor immunosuppressive microenvironment and inhibit tumor growth,which is expected to be The treatment of spinal metastases provides new methods and concepts.Methods: This experiment combines radiotherapy with immunotherapy,and induces immunogenic death of mouse tumor cells through radiotherapy,and synergizes with the immunomodulator IL-12 and the TGF-β inhibitor SB-431542 carried by the hydrogel to achieve the Tumor immunosuppressive microenvironment regulation and inhibit tumor growth.Result:(1)Material synthesis The drug-loaded composite hydrogel achieves sustained and slow drug delivery in the tumor in situ.(2)Cell experiment In vitro cell experiments have shown that radiotherapy can induce immunogenic death of mouse tumor cells,and that the cellular immunogenicity is highest when the dose of radiotherapy is 10 Gy.(3)Animal experiment In vivo experiments have shown that radiotherapy can induce immunogenic death of mouse tumor cells,reverse the immunosuppressive microenvironment of mouse tumor sites,and improve the effect of immunotherapy.Local radiotherapy combined with immunotherapy improves the proliferation and activation of T cells at tumor sites in mice;inhibits the TGF-β signaling pathway,reduces the infiltration of Treg cells in the tumor site;promotes the proliferation of DC cells and improves the tumor site Antigen presentation.Significantly inhibited tumor growth in mice,improved spinal cord compression and bone destruction at the tumor site.Conclusion: Radiotherapy induces immunogenic death of mouse tumor cells and reverses the microenvironment of tumor immunosuppression.In addition,the hydrogel drug delivery system realizes the sustained and slow release of immunomodulators in situ.The synergistic effect of the two increased the infiltration of CD8+ T cells at the tumor site in mice,and significantly delayed the growth of breast cancer spinal metastases in mice.