基于Fe-Pt异核双原子活性位点协同催化体系构建及其在纳米催化医学领域应用探索

本项目依据“纳米催化医学”设计理念，将亚纳米结构材料“高效率、高选择”的优异催化性能应用到肿瘤诊疗方面，以实现对肿瘤“高治疗效率、低毒副作用”的目的。通过对MOFs材料吸附位点的精准设计，建立一种普适的异核双原子活性位点（Fe1，Pt1~x）-SAs/NC协同催化体系构建新策略，实现对Fe、Pt单原子浓度、几何结构的精准控制，揭示其在原子尺度的成核和生长行为。构建小鼠肿瘤模型，研究基于Fe SACs “铁死亡”抑瘤、Pt1~x催化内源H2O2分解供氧协同抑瘤机制。通过与免疫佐剂（CpG ODNs）、免疫检查点抑制剂(anti-CTLA4等)联用，揭示对局部肿瘤的“铁死亡”抑制触发免疫“记忆效应“与“远端效应”的协同增效机制。通过本项目的实施，发展一种高效、高特异性的纳米催化诊疗试剂，实现既能催化化疗抑制原发肿瘤，又能触发免疫反应的目的，为构建新型肿瘤诊疗平台提供理论支撑和实验依据。

Based on the “Nanocatalytic Medicine” design concept, the excellent catalytic performance of “high efficiency and high selection”of sub-nano structure materials is applied in tumor diagnosis and treatment to achieve the goal of high treatment efficiency and low toxic side effects. Through the precise design of the adsorption sites of MOFs materials, a new strategy of synergistic catalytic system of heteronuclear diatomic active sites（Fe1，Pt1~x）-SAs/NC was established to accomplish the precise control of single atoms concentration and geometric structure, and to reveal the nucleation and growth behavior at the atomic scale. A tumor-bearing mice model was constructed to study synergistic tumor suppressor mechanism based on Fe SACs ferroptosis and Pt1~x catalytic endogenous H2O2 decomposition for oxygen supply. Immune adjuvants (CpG ODNs) and immune checkpoint inhibitors (anti-CTLA4, etc.) were also combined in this research to reveal synergistic mechanism between the immunotherapy triggered by “memory effect” and “distant effect” and chemotherapy triggered by ferroptosis. . Through the implementation of this project, a novel heteronuclear diatomic active sites（Fe1，Pt1~x）-SAs/NC nanocatalytic diagnostic and therapeutic reagent with high efficiency and specificity could be constructed and achieved the aim of not only catalyzing chemotherapy to suppress the primary tumor but also triggering the immune response. We hope to provide theoretical support and experimental basis for building a new type of tumor diagnostic and therapeutic platform.