第二近红外光增强的活性氧用于肿瘤联合治疗及其作用机制研究

晚期肿瘤缺乏有效的治疗手段，导致其致死率长期居高不下。尽管基于单一活性氧（ROS）的多种新型肿瘤疗法具有非侵入性、可忽略的毒副作用等优点，其效果仍不理想。因此，设计基于多种ROS的肿瘤联合疗法，具有重要的科学研究价值和广阔的应用前景。本项目提出利用NIR-II光增强多种ROS产生的联合诊疗策略：1）构建自掺杂钨酸铁（FeWO4-x），利用其在NIR-II区的强吸收和半导体性质以及温和的光热效应，促进多种ROS的产生，实现NIR-II光增强的多种ROS联合治疗。2）探索多种ROS联合治疗的反应动力学、反应机制和损伤分子机制，阐明NIR-II光增强的多种ROS联合治疗的理论。预实验已初步合成该自掺杂材料，本项目的完成有望提高对晚期肿瘤的治疗效果，为基于ROS的肿瘤联合治疗策略提供新材料和思路。

The mortality of advanced malignant tumors has remained high due to the lack of effective treatments. Despite various of tumor therapies based on reactive oxygen species (ROS) exhibit the advantages such as non-invasive and negligible side effects, the therapeutic effect of monotherapy is still not ideal. Therefore, the design of multiple ROS-based tumor combination therapy has important research value and broad application prospects. In this project, we propose the strategy to promote multiple ROS generation by NIR-II light for combination therapy: 1) Construct a simple self-doped iron tungstate (FeWO4-x) with strong NIR-II absorption. On one hand, the NIR-II irradiation can promote ROS production by energy/electron transfer and photo-enhanced Fenton reaction; on the other hand, the mild NIR-II photothermal effect can further enhance the generation of multiple ROS, so as to synergize the therapeutic effect. 2) Investigate the reaction kinetics, reaction mechanism and apoptotic mechanism to elucidate the rationale of this NIR-II light enhanced multiple ROS-based combination therapy. The self-doping FeWO4-x has been synthesized in preliminary experiments. The project is expected to improve the therapeutic effect for advanced tumors and provide new materials and research ideas for ROS-based combinatorial therapy strategies.