新型纳米材料NMOFs在放化疗联合anti-TIM3治疗NSCLC机制的研究

肺癌是全世界范围内发病率最高的恶性肿瘤，5年生存率低于18%。本项目组构建的金属有机框架纳米材料（NMOFs）因其独特的理化性质和结构，具有强大负载能力和天然的生物可降解性及较好的肿瘤靶向性，可作为免疫治疗药物和化疗药物的良好载体。本项目拟通过多个非小细胞肺癌细胞系、皮下荷瘤和肺部自发肿瘤小鼠模型，研究NMOFs放射增敏作用及机制，探讨NMOFs-α-TIM3联合放化疗治疗非小细胞肺癌的的疗效，应用实时荧光定量和免疫印迹技术检测肿瘤细胞和树突状细胞胞内cGAS-MITA通路的相关分子与IFN-I的表达量，采用MITA抑制剂进行回复实验，探讨cGAS-MITA通路的激活是否是NMOFs-α-TIM3联合放化疗治疗非小细胞肺癌的作用机理。本项目旨在探索NMOFs-α-TIM3联合放化疗治疗非小细胞肺癌免疫调控机制和新的免疫治疗途径。

Lung cancer is the most common malignancy worldwide, with a 5-year survival rate of less than 18%. Due to its unique physical and chemical properties, the nanoscale metal-organic frameworks (NMOFs) have high loading capacity, natural biodegradability and good tumor-targeting ability, as a good carrier for immunotherapy and chemotherapy drugs. Using multiple non-small cell lung cancer cell lines, subcutaneous tumor-burdened and spontaneous lung tumor mouse model, this project intends to study NMOF radiosensitization and its mechanism, and to explore curative effects of NMOFs-α-TIM3 in the combination of radiochemotherapy and immunotherapy for non-small cell lung cancer. Intracellular cGAS-MITA pathways related molecules and the expression of IFN-I are detected with real-time quantitation and immunoblotting in tumor cells and dendritic cells. Using MITA inhibitors for rescue experiments, we investigate whether the activation of cGAS-MITA pathway moldulates α-TIM3 combined with chemoradiotherapy in the treatment of non-small cell lung cancer. This project aims to explore the immunoregulation mechanism and novel immunotherapy approaches of NMOFs-α-TIM3 combined with chemoradiotherapy in the treatment of lung cancer.