Chemodynamic therapy (CDT) is an appealing cancer treatment that converts endogenous H₂O₂ into highly toxic hydroxyl radicals to kill cancer cells. However, the limited amount of H₂O₂ in tumor cells constrains the application of CDT. Therefore, the strategy that can increase H₂O₂ level in situ could broaden its clinical application. Herein, we synthesized a supramolecule [Ru(bpy)₂(Nabpy)](PF₆)₂ (Ru1) which can efficiently photo-catalyze NAD(P)H oxidation with simultaneous generation of H₂O₂ with a high yield at 76.4 %. The Ru1 and Fe²⁺ were then loaded on the mesoporous silica-encapsulated rare earth-doped upconversion nanoparticles (UCSRF), the intracellular H₂O₂ level can be elevated by 2.8 times upon the irradiation of near-infrared (NIR) light irradiation. Then, the intracellular H₂O₂ was transformed into hydroxyl radicals through Fenton reaction to achieve efficient CDT both in vitro and in vivo. Furthermore, we demonstrated that UCSRF could effectively enhance immunogenic cell death (ICD) effect, resulting in the reprogramming of the immunosuppressive tumor microenvironment to stimulate immune response. This work represents the first proof-of-concept study on photo-catalytically enhancing H₂O₂ production in situ upon NIR irradiation for spatiotemporal CDT.

化学动力学疗法 (CDT) 是一种有吸引力的癌症治疗方法，可将内源性 H ₂ O ₂转化为剧毒的羟基自由基以杀死癌细胞。_{然而，肿瘤细胞中H 2} O ₂的含量有限限制了CDT的应用。因此，原位提高H ₂ O ₂水平的策略可以拓宽其临床应用。在此，我们合成了一种超分子 [Ru(bpy) ₂ (Nabpy)](PF ₆ ) ₂ (Ru1)，它可以有效地光催化 NAD(P)H 氧化并同时生成 H ₂ O ₂收率高达 76.4%。然后将Ru1和Fe ²⁺负载到介孔二氧化硅包封的稀土掺杂上转换纳米颗粒（UCSRF）上，在近红外（NIR）光照射下，细胞内H ₂ O ₂水平可提高2.8倍. 然后，通过芬顿反应将细胞内的H ₂ O ₂转化为羟基自由基，从而在体外和体内实现高效的CDT. 此外，我们证明 UCSRF 可以有效增强免疫原性细胞死亡 (ICD) 效应，从而导致免疫抑制性肿瘤微环境的重新编程以刺激免疫反应。这项工作代表了第一个关于在 NIR 照射时空 CDT 时光催化增强原位 H ₂ O ₂产生的概念验证研究。