Quasi Fe MIL-53 nanozyme inducing ferroptosis and immunogenic cell death for cancer immunotherapy

• Published in: Nature communications Vol. 16; no. 1; pp. 2290 - 19
• Main Authors: Yan, Zihui, Bai, Yang, Zhang, Songtao, Kong, Lingyi, Wang, Yu, Sun, Huilin, Li, Yi, Qiu, Lin, Zhang, Ruijie, Jiang, Pengju, Zhao, Donghui, Chen, Zhongyan, Li, Yafei, Pang, Huan, Wang, Jianhao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.03.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 13/95; 14/19; 38/91; 639/301/54/990; 639/638/263/49; Animals; Anticancer properties; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Biocompatibility; Cancer; Cancer immunotherapy; Cancer therapies; Catalase; Cell death; Cell Line, Tumor; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Density functional theory; Depletion; Female; Ferroptosis; Ferroptosis - drug effects; Glutathione; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunogenic Cell Death - drug effects; Immunogenicity; Immunotherapy; Immunotherapy - methods; Iron; Iron - chemistry; Lymphocytes; Lymphocytes T; Metal oxides; Metal-organic frameworks; Metal-Organic Frameworks - chemistry; Metal-Organic Frameworks - pharmacology; Metals; Metastases; Mice; Mortality; multidisciplinary; Nanomaterials; Nanostructures - chemistry; Nanotechnology; Neoplasms - immunology; Neoplasms - therapy; PD-1 protein; Peroxidase; Science; Science (multidisciplinary)
• DOI: 10.1038/s41467-025-57542-x
• ISSN: 2041-1723

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 glutathione 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. Nanozymes offer diverse therapeutic avenues for cancer treatment. In this work, the authors report an iron-based quasi-metal organic framework nanozyme Q-MIL-53(Fe) with enhanced peroxidase and catalase-mimicking activity and glutathione depletion capacity and use it for tumor immunotherapy via inducing ferroptosis and immunogenic cell death.