含有氧缺陷的氧化铋纳米片在肿瘤放疗增敏以及免疫治疗中的应用研究

本项目以推动“免疫放疗”在肿瘤治疗中的应用为目标，构建新型具有过氧化氢酶活性的超薄BiO2-x纳米片，利用其独特的物理化学性质提高肿瘤细胞放疗敏感性，激活肿瘤特异性免疫反应，实现在较低的放射剂量下既能抑制原位肿瘤又能激活肿瘤特异性免疫反应实现对转移肿瘤抑制。BiO2-x纳米片中含有高原子序数元素Bi，可以吸收高能射线，促进细胞内活性氧（ROS）的生成，实现放疗物理增敏；同时BiO2-x纳米片还可以催化肿瘤微环境中H2O2产生氧气，改善肿瘤内部乏氧，诱导肿瘤相关巨噬细胞（TAM）向M1型极化，提高肿瘤抑制效率。另外，BiO2-x纳米片放疗增敏过程中产生的ROS会诱导肿瘤细胞免疫原性死亡，提高肿瘤部位抗原呈递效率，增敏免疫治疗。利用BiO2-x纳米片放疗增敏以及H2O2催化特性，探索放疗与免疫治疗的有机结合，并阐释对肿瘤放疗与免疫治疗增敏机制，为临床肿瘤“免疫放疗”治疗提供一个新的思路。

This project aims to promote the application of "immunoradiotherapy" in the treatment of tumors, to construct new ultra-thin BiO2-x nanosheets with catalase activity, and to use its unique physical and chemical properties to improve the sensitivity of tumor cells to radiotherapy and activate tumor specific immune response, which can not only inhibit tumor in situ but also activate tumor specific immune response to achieve suppression of metastatic tumors at a lower radiation dose. BiO2-x nanosheets contain a high atomic number element Bi, which can absorb high-energy rays, promote the generation of intracellular reactive oxygen species (ROS), and achieve radiotherapy physical sensitization. At the same time, BiO2-x nanosheets can decompose the highly-expressed hydrogen peroxide at tumor site into oxygen for combating hypoxia, induces the polarization of tumor-associated macrophages (TAM) to the M1 type, and improves the tumor suppression efficiency. In addition, the ROS generated during the radiosensitization process of BiO2-x nanosheets can induce the immunogenic death of tumor cells, increase the efficiency of antigen presentation at the tumor site, and enhance the sensitivity of immunotherapy. Using BiO2-x nanosheet radiotherapy sensitization and H2O2 catalytic properties, in this project, we try to explore the combination of radiotherapy and immunotherapy, and to explain the mechanism of tumor radiotherapy and immunotherapy sensitization, to provide a new idea for clinical tumor "immunoradiotherapy" treatment.