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Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination

Tumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off‐target toxicity. Herein, a multifunctional cascade biore...

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Autores principales: Xiong, Yuxuan, Yong, Zhengtao, Xu, Chen, Deng, Qingyuan, Wang, Qiang, Li, Shiyou, Wang, Chong, Zhang, Zhijie, Yang, Xiangliang, Li, Zifu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375084/
https://www.ncbi.nlm.nih.gov/pubmed/37114827
http://dx.doi.org/10.1002/advs.202301278
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author Xiong, Yuxuan
Yong, Zhengtao
Xu, Chen
Deng, Qingyuan
Wang, Qiang
Li, Shiyou
Wang, Chong
Zhang, Zhijie
Yang, Xiangliang
Li, Zifu
author_facet Xiong, Yuxuan
Yong, Zhengtao
Xu, Chen
Deng, Qingyuan
Wang, Qiang
Li, Shiyou
Wang, Chong
Zhang, Zhijie
Yang, Xiangliang
Li, Zifu
author_sort Xiong, Yuxuan
collection PubMed
description Tumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off‐target toxicity. Herein, a multifunctional cascade bioreactor (HCG), based on the self‐assembly of pH‐responsive hydroxyethyl starch prodrugs, copper ions, and glucose oxidase (GOD), is engineered, empowered by hyperbaric oxygen (HBO) for efficient cooperative therapy against aggressive breast cancers. Once internalized by tumor cells, HCG undergoes disassembly and releases cargoes in response to acidic tumor microenvironment. Subsequently, HBO activates GOD‐catalyzed oxidation of glucose to H(2)O(2) and gluconic acid by ameliorating tumor hypoxia, fueling copper‐catalyzed •OH generation and pH‐responsive drug release. Meanwhile, HBO degrades dense tumor extracellular matrix, promoting tumor accumulation and penetration of HCG. Moreover, along with the consumption of glucose and the redox reaction of copper ions, the antioxidant capacity of tumor cells is markedly reduced, collectively boosting oxidative stress. As a result, the combination of HCG and HBO can not only remarkably suppress the growth of orthotopic breast tumors but also restrain pulmonary metastases by inhibiting cancer stem cells. Considering the clinical accessibility of HBO, this combined strategy holds significant translational potentials for GOD‐based therapies.
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spelling pubmed-103750842023-07-29 Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination Xiong, Yuxuan Yong, Zhengtao Xu, Chen Deng, Qingyuan Wang, Qiang Li, Shiyou Wang, Chong Zhang, Zhijie Yang, Xiangliang Li, Zifu Adv Sci (Weinh) Research Articles Tumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off‐target toxicity. Herein, a multifunctional cascade bioreactor (HCG), based on the self‐assembly of pH‐responsive hydroxyethyl starch prodrugs, copper ions, and glucose oxidase (GOD), is engineered, empowered by hyperbaric oxygen (HBO) for efficient cooperative therapy against aggressive breast cancers. Once internalized by tumor cells, HCG undergoes disassembly and releases cargoes in response to acidic tumor microenvironment. Subsequently, HBO activates GOD‐catalyzed oxidation of glucose to H(2)O(2) and gluconic acid by ameliorating tumor hypoxia, fueling copper‐catalyzed •OH generation and pH‐responsive drug release. Meanwhile, HBO degrades dense tumor extracellular matrix, promoting tumor accumulation and penetration of HCG. Moreover, along with the consumption of glucose and the redox reaction of copper ions, the antioxidant capacity of tumor cells is markedly reduced, collectively boosting oxidative stress. As a result, the combination of HCG and HBO can not only remarkably suppress the growth of orthotopic breast tumors but also restrain pulmonary metastases by inhibiting cancer stem cells. Considering the clinical accessibility of HBO, this combined strategy holds significant translational potentials for GOD‐based therapies. John Wiley and Sons Inc. 2023-04-28 /pmc/articles/PMC10375084/ /pubmed/37114827 http://dx.doi.org/10.1002/advs.202301278 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Xiong, Yuxuan
Yong, Zhengtao
Xu, Chen
Deng, Qingyuan
Wang, Qiang
Li, Shiyou
Wang, Chong
Zhang, Zhijie
Yang, Xiangliang
Li, Zifu
Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
title Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
title_full Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
title_fullStr Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
title_full_unstemmed Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
title_short Hyperbaric Oxygen Activates Enzyme‐Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination
title_sort hyperbaric oxygen activates enzyme‐driven cascade reactions for cooperative cancer therapy and cancer stem cells elimination
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375084/
https://www.ncbi.nlm.nih.gov/pubmed/37114827
http://dx.doi.org/10.1002/advs.202301278
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