Source data of Quasi Fe MIL-53 Nanozyme Inducing Ferroptosis and Immunogenic Cell Death for Cancer Immunotherapy

Nanozymes offer diverse therapeutic potentials for cancer treatment which is dependent on the development of nanomaterials. Quasi-metal-organic framework is a class of metal-organic framework-derived nanomaterials with a transition state from metal-organic frameworks towards metal oxide featuring porous structure and high activity. Herein an iron-based quasi-metal-organic framework nanozyme Q-MIL-53(Fe) is reported via a controlled deligandation strategy, exhibiting enhanced peroxidase-/catalase-mimic activity and GSH depletion capacity, whose underlying mechanisms are studied via Density Functional Theory calculations. Q-MIL-53(Fe) demonstrates biocompatibility and superior antitumor efficacy compared to pristine MIL-53(Fe). It can activate antitumor immune response by inducing ferroptosis and immunogenic cell death, promoting dendritic cell maturation and T lymphocytes infiltration. Furthermore, a combination of Q-MIL-53(Fe) and programmed cell death protein 1 antibody amplifies cancer immunotherapy. This study validates the antitumor activity of quasi-metal-organic frameworks and its immunotherapy induction potential. It would broaden the application of quasi-metal-organic frameworks and open avenues for developing antitumor nanozymes.

纳米酶（nanozymes）在癌症治疗中展现出多样的治疗潜力，而其应用发展有赖于纳米材料的研发进步。准金属有机框架（quasi-metal-organic framework, QMOF）是一类由金属有机框架衍生而来的纳米材料，处于金属有机框架向金属氧化物的过渡状态，兼具多孔结构与高催化活性。本文通过可控脱配体策略，制备了一种铁基准金属有机框架纳米酶Q-MIL-53(Fe)，其展现出增强的过氧化物酶/过氧化氢酶模拟活性与谷胱甘肽（GSH）耗竭能力，本研究通过密度泛函理论（Density Functional Theory, DFT）计算对其潜在作用机制进行了探究。与原始MIL-53(Fe)相比，Q-MIL-53(Fe)展现出良好的生物相容性与更优异的抗肿瘤效果。该纳米酶可通过诱导铁死亡与免疫原性细胞死亡，促进树突状细胞成熟与T淋巴细胞浸润，从而激活抗肿瘤免疫应答。此外，将Q-MIL-53(Fe)与程序性死亡蛋白1（programmed cell death protein 1, PD-1）抗体联合使用，可增强癌症免疫治疗效果。本研究验证了准金属有机框架的抗肿瘤活性及其诱导免疫治疗的潜力，有望拓展准金属有机框架的应用场景，同时为抗肿瘤纳米酶的开发开辟新路径。