基于新型二维纳米载体的化学动力学/光热协同疗法诱导Ferroptosis/Oxeiptosis杀伤肝癌细胞的作用及机制研究

肝癌是最常见且恶性程度很高的恶性肿瘤之一，中晚期肝癌缺乏有效疗法是制约肝癌患者长期生存的瓶颈所在，迫切需要开发高效的肝癌治疗手段。纳米材料在医学应用中的快速发展，为改善肝癌的预后提供了机遇。二维MXene作为新型的光热材料，由近红外光激发后将光能转化为热能从而杀伤肿瘤，MXene还可以作为靶向运载体，实现肿瘤微环境响应型输送和释放。基于上述特性，本课题拟将超小氧化铁粒子和GOD酶共负载于Mxene上，构建化学动力学和光热疗法相结合纳米复合体GE@MXene，利用材料表征、分子和动物实验等方法，观察GE@MXene生物安全性和体内外抗肝癌效果。本课题拟进一步对GE@MXene杀伤肝癌细胞的机制进行研究，探索铁死亡和Oxeiptosis机制在GE@Mxene杀伤肝癌细胞过程中的作用，为阐明GE@MXene诱导肝癌死亡的机制提供科学依据，也从细胞死亡机制角度为优化抗肝癌策略提供新的靶点和思路。

Hepatocellular carcinoma (HCC) is one of the most common and highly malignant tumors. The lack of effective therapy for advanced HCC is the bottleneck which restricts the long-term survival of patients with HCC. There is an urgent need to develop efficient treatment for HCC. The rapid development of nanomaterials in medical application provides an opportunity to improve the prognosis of HCCs. As a new type of photothermal material, two-dimensional MXene can transform light energy into heat energy after being irradiated by near-infrared light, so as to kill tumor. MXene can also served as a targeted carrier to achieve responsive transport and release of tumor microenvironment. Based on the above characteristics, we intend to co-load extremely small-sized iron oxide nanoparticles and GOD enzyme on Mxene to construct nanocomposites “GE@MXene” combining chemodynamic therapy and photothermal therapy. The biological safety and anti-HCC effect of GE@MXene in vivo and in vitro are evaluated by means of material characterization, molecular and animal experiments. This study intends to make a further research on the mechanism of GE@MXene killing HCC cells. This study explored the roles of Ferroptosis and Oxeiptosis in the process of killing HCC cells, which provides scientific basis for elucidating the mechanism of GE@MXene-induced HCC death, and new targets and ideas for optimizing anti-HCC strategies from the perspective of cell death mechanism.