Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor.

Kai Zhang, Zhaoyu Ma, Shuting Li, Yang Wu, Jin Zhang, Weiyun Zhang, Yanli Zhao, Heyou Han

Biomaterials 2022 May

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Ferroptosis, a newfound non-apoptotic cell death pathway that is iron- and reactive oxygen species (ROS)-dependent, has shown a promise for tumor treatment. However, engineering ferroptosis inducers with sufficient hydrogen peroxide (H2O2) and iron supplying capacity remains a great challenge. To address this issue, herein, we report a powerful nanoreactor by modifying MnO2, glucose oxidase, and polyethylene glycol on iron-based metal-organic framework nanoparticles for disrupting redox and iron metabolism homeostasis, directly providing the Fenton reaction-independent downstream ferroptosis for tumor therapy. By consuming glutathione and oxidizing glucose to increase the H2O2 level in cancer cells and downregulating ferroportin 1 to accumulate intracellular iron ions, the homeostasis disruptor could effectively enhance the ferroptosis. Subsequently, the ferroptosis cells release tumor immune-associated antigens, which combine with in situ injected aptamer-PD-L1 to further strengthen the tumor treatment efficiency. This work not only paves a way to enhance the efﬁcacy of ferroptosis-based cancer therapy by associating intracellular redox homeostasis with the iron metabolism system in tumor cells but also offers an engineered nanoreactor as a promising mimetic antigen for activating immunotherapy. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Kai Zhang, Zhaoyu Ma, Shuting Li, Yang Wu, Jin Zhang, Weiyun Zhang, Yanli Zhao, Heyou Han. Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor. Biomaterials. 2022 May;284:121502