铁死亡是索拉非尼介导肝细胞癌肿瘤细胞死亡的重要方式；NRF2是导致索拉非尼铁死亡治疗抵抗的关键因素；联合铁剂的光热治疗可通过Fenton反应和谷胱甘肽消耗来促进铁死亡的发生。我们前期研究表明，联合光热治疗的ZIF纳米递药系统可以有效促进肿瘤内药物富集，发挥化疗-光热协同治疗的作用。本项目拟构建具备肿瘤微环境响应性、光热效应、负载铁剂的双药联载纳米递药系统；研究NRF2抑制剂和索拉非尼的药物组合方案在促进肝细胞癌铁死亡中的作用与机制；明确基于新型双药联载纳米递药系统的分子靶向-光热协同治疗在促进肝癌细胞铁死亡、增强索拉非尼疗效中的作用。本项目的研究成果可以为肝细胞癌的多学科综合治疗提供理论依据和有效策略。

Ferroptosis is an important way of tumor cell death induced by sorafenib in hepatocellular carcinoma. NRF2 is an important factor in resistance to ferroptosis induced by sorafenib. Combined with chalybeate, photothermal therapy can promote ferroptosis through glutathione depletion and Fenton reaction. Our previous studies have shown that the ZIF nano-delivery system combined with photothermal therapy can effectively promote drug delivery and exert the synergistic effect of molecular targeted therapy and photothermal therapy. This project intends to construct a dual-drug delivery system with tumor microenvironmental responsiveness, photothermal effect and chalybeate loaded. This project intends to investigate the function and mechanism of NRF2 inhibitor and sorafenib in collaboratively promoting ferroptosis in hepatocellular carcinoma. This project intends to confirm the synergistic effect of molecular targeted therapy and photothermal therapy based on the novel dual-drug delivery system in promoting ferroptosis and enhancing the efficacy of sorafenib in hepatocellular carcinoma. The results of this project can provide a new theoretical basis and an effective strategy for the multidisciplinary comprehensive treatment of hepatocellular carcinoma.