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

Zihui Yan, Yang Bai (), Songtao Zhang, Lingyi Kong, Yu Wang, Huilin Sun, Yi Li, Lin Qiu, Ruijie Zhang, Pengju Jiang, Donghui Zhao, Zhongyan Chen, Yafei Li (), Huan Pang () and Jianhao Wang ()
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Zihui Yan: Changzhou University
Yang Bai: Changzhou University
Songtao Zhang: Yangzhou University
Lingyi Kong: Nanjing Normal University
Yu Wang: Nanjing Normal University
Huilin Sun: Changzhou University
Yi Li: Changzhou University
Lin Qiu: Changzhou University
Ruijie Zhang: Changzhou University
Pengju Jiang: Changzhou University
Donghui Zhao: Changzhou University
Zhongyan Chen: Wenzhou University
Yafei Li: Changzhou University
Huan Pang: Yangzhou University
Jianhao Wang: Changzhou University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-57542-x

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