Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses
Hypoxia, a prevalent characteristic of solid tumors, substantially impairs the efficacy of cancer treatments. However, there are no feasible clinical approaches for treating hypoxic tumors. Here, we develop metal-phenolic networks (CuGI) utilizing the natural glycolysis inhibitor (epigallocatechin g...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-05-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25000222 |
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| author | Jia Liu Zuoyu Chen Lixue Deng Chundong Yao Zhixin Zhou Cheng Zhou Yawen Bin Miaodeng Liu Liping Wang Lin Wang Zheng Wang |
| author_facet | Jia Liu Zuoyu Chen Lixue Deng Chundong Yao Zhixin Zhou Cheng Zhou Yawen Bin Miaodeng Liu Liping Wang Lin Wang Zheng Wang |
| author_sort | Jia Liu |
| collection | DOAJ |
| description | Hypoxia, a prevalent characteristic of solid tumors, substantially impairs the efficacy of cancer treatments. However, there are no feasible clinical approaches for treating hypoxic tumors. Here, we develop metal-phenolic networks (CuGI) utilizing the natural glycolysis inhibitor (epigallocatechin gallate) and the essential metal element in the human body (copper ions), specifically targeting and annihilating hypoxic cancer cells. CuGI redirects the metabolic pathway of hypoxic cancer cells from anaerobic glycolysis to oxidative phosphorylation, thereby enhancing reactive oxygen species production and promoting oligomerization of lipoylated proteins in the tricarboxylic acid cycle. Through targeted induction of oxidative and proteotoxic stresses, CuGI induces apoptosis and cuproptosis specifically in cancer cells under hypoxic conditions while sparing normal cells. Moreover, cancer cell membrane-coated CuGI (CuGI@CM) exhibits enhanced tumor penetration effect and demonstrates commendable biocompatibility, effectively suppressing colorectal tumor growth. Importantly, CuGI@CM, when combined with vascular disruptors or radiotherapy which aggravate tumor hypoxia, synergistically potentiates therapeutic efficacy. Thus, CuGI represents a specific and potent nanotherapeutic capable of selectively eliminating hypoxic tumors, offering promise in combination therapies to address tumor hypoxia. |
| format | Article |
| id | doaj-art-8fc3c264532a4d2595e25bf3f8596a97 |
| institution | DOAJ |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-8fc3c264532a4d2595e25bf3f8596a972025-08-20T03:12:38ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-014736137710.1016/j.bioactmat.2025.01.022Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stressesJia Liu0Zuoyu Chen1Lixue Deng2Chundong Yao3Zhixin Zhou4Cheng Zhou5Yawen Bin6Miaodeng Liu7Liping Wang8Lin Wang9Zheng Wang10Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Provincial Engineering Research Center of Clinical Laboratory and Active Health Smart Equipment, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Corresponding author. Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaResearch Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaResearch Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaResearch Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaHubei Key Laboratory of Precision Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaResearch Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaResearch Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, ChinaResearch Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Provincial Engineering Research Center of Clinical Laboratory and Active Health Smart Equipment, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Corresponding author. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Provincial Engineering Research Center of Clinical Laboratory and Active Health Smart Equipment, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Corresponding author. Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.Hypoxia, a prevalent characteristic of solid tumors, substantially impairs the efficacy of cancer treatments. However, there are no feasible clinical approaches for treating hypoxic tumors. Here, we develop metal-phenolic networks (CuGI) utilizing the natural glycolysis inhibitor (epigallocatechin gallate) and the essential metal element in the human body (copper ions), specifically targeting and annihilating hypoxic cancer cells. CuGI redirects the metabolic pathway of hypoxic cancer cells from anaerobic glycolysis to oxidative phosphorylation, thereby enhancing reactive oxygen species production and promoting oligomerization of lipoylated proteins in the tricarboxylic acid cycle. Through targeted induction of oxidative and proteotoxic stresses, CuGI induces apoptosis and cuproptosis specifically in cancer cells under hypoxic conditions while sparing normal cells. Moreover, cancer cell membrane-coated CuGI (CuGI@CM) exhibits enhanced tumor penetration effect and demonstrates commendable biocompatibility, effectively suppressing colorectal tumor growth. Importantly, CuGI@CM, when combined with vascular disruptors or radiotherapy which aggravate tumor hypoxia, synergistically potentiates therapeutic efficacy. Thus, CuGI represents a specific and potent nanotherapeutic capable of selectively eliminating hypoxic tumors, offering promise in combination therapies to address tumor hypoxia.http://www.sciencedirect.com/science/article/pii/S2452199X25000222Tumor hypoxiaMetal-organic networksCell metabolismReactive oxygen speciesCuproptosis |
| spellingShingle | Jia Liu Zuoyu Chen Lixue Deng Chundong Yao Zhixin Zhou Cheng Zhou Yawen Bin Miaodeng Liu Liping Wang Lin Wang Zheng Wang Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses Bioactive Materials Tumor hypoxia Metal-organic networks Cell metabolism Reactive oxygen species Cuproptosis |
| title | Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses |
| title_full | Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses |
| title_fullStr | Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses |
| title_full_unstemmed | Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses |
| title_short | Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses |
| title_sort | metal phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses |
| topic | Tumor hypoxia Metal-organic networks Cell metabolism Reactive oxygen species Cuproptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25000222 |
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