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Title: Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
Authors: Zhang, Kai
Ma, Zhaoyu
Li, Shuting
Wu, Yang
Zhang, Jin
Zhang, Weiyun
Zhao, Yanli
Han, Heyou
Keywords: Science::Chemistry::Biochemistry
Issue Date: 2022
Source: Zhang, K., Ma, Z., Li, S., Wu, Y., Zhang, J., Zhang, W., Zhao, Y. & Han, H. (2022). Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor. Biomaterials, 284, 121502-.
Journal: Biomaterials
Abstract: 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.
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2022.121502
Schools: School of Physical and Mathematical Sciences 
Rights: © 2022 Elsevier Ltd. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SPMS Journal Articles

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