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

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 ad...

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Main Authors: Zhang, Kai, Ma, Zhaoyu, Li, Shuting, Wu, Yang, Zhang, Jin, Zhang, Weiyun, Zhao, Yanli, Han, Heyou
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/161844
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1618442022-09-21T06:26:40Z Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor Zhang, Kai Ma, Zhaoyu Li, Shuting Wu, Yang Zhang, Jin Zhang, Weiyun Zhao, Yanli Han, Heyou School of Physical and Mathematical Sciences Science::Chemistry::Biochemistry Dual Homeostasis Ferroptosis 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. This work was supported by the National Key R & D Program of China (2021YFD1400800), and the National Natural Science Foundation of China (21778020 and 21804046). 2022-09-21T06:26:40Z 2022-09-21T06:26:40Z 2022 Journal Article 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-. https://dx.doi.org/10.1016/j.biomaterials.2022.121502 0142-9612 https://hdl.handle.net/10356/161844 10.1016/j.biomaterials.2022.121502 35390708 2-s2.0-85127521031 284 121502 en Biomaterials © 2022 Elsevier Ltd. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry::Biochemistry
Dual Homeostasis
Ferroptosis
spellingShingle Science::Chemistry::Biochemistry
Dual Homeostasis
Ferroptosis
Zhang, Kai
Ma, Zhaoyu
Li, Shuting
Wu, Yang
Zhang, Jin
Zhang, Weiyun
Zhao, Yanli
Han, Heyou
Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
description 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.
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Zhang, Kai
Ma, Zhaoyu
Li, Shuting
Wu, Yang
Zhang, Jin
Zhang, Weiyun
Zhao, Yanli
Han, Heyou
format Article
author Zhang, Kai
Ma, Zhaoyu
Li, Shuting
Wu, Yang
Zhang, Jin
Zhang, Weiyun
Zhao, Yanli
Han, Heyou
author_sort Zhang, Kai
title Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
title_short Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
title_full Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
title_fullStr Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
title_full_unstemmed Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
title_sort disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor
publishDate 2022
url https://hdl.handle.net/10356/161844
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