Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells
ABSTRACT An extracellular acidic environment and an intracellular mildly alkaline environment induced by carbonic anhydrase 9 (CA9) play a critical role in self‐renewal, invasion, migration, and drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report an antitumor str...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Exploration |
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| Online Access: | https://doi.org/10.1002/EXP.20240080 |
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| author | Qingyuan Deng Ao Hua Shiyou Li Zhijie Zhang Xiang Chen Qiang Wang Xing Wang Zhiqin Chu Xiangliang Yang Zifu Li |
| author_facet | Qingyuan Deng Ao Hua Shiyou Li Zhijie Zhang Xiang Chen Qiang Wang Xing Wang Zhiqin Chu Xiangliang Yang Zifu Li |
| author_sort | Qingyuan Deng |
| collection | DOAJ |
| description | ABSTRACT An extracellular acidic environment and an intracellular mildly alkaline environment induced by carbonic anhydrase 9 (CA9) play a critical role in self‐renewal, invasion, migration, and drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report an antitumor strategy leveraging hyperbaric oxygen therapy (HBO) to regulate tumor pH and boost hydroxyethyl starch‐doxorubicin‐copper nanoparticles (HHD‐Cu NPs) against CSCs. HBO overcomes tumor hypoxia, downregulates pH‐regulatory proteins such as CA9, and leads to intracellular accumulation of acidic metabolites. As a result, HBO promotes intracellular acidification of both tumor cells and CSCs, triggering efficient doxorubicin release and the potent copper‐mediated chemical dynamic effect of subsequently administered dual‐acid‐responsive HHD‐Cu NPs. The combination of HBO with HHD‐Cu NPs not only eliminates tumor cells but also inhibits CSCs, altogether leading to potent tumor inhibition. This study explores a new function of clinical‐widely used HBO and establishes a novel combination therapy for treating CSCs abundant hypoxic solid tumors. |
| format | Article |
| id | doaj-art-c345bcb8501f4749ae885b574df396d0 |
| institution | Kabale University |
| issn | 2766-8509 2766-2098 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Exploration |
| spelling | doaj-art-c345bcb8501f4749ae885b574df396d02025-08-26T10:32:53ZengWileyExploration2766-85092766-20982025-08-0154n/an/a10.1002/EXP.20240080Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem CellsQingyuan Deng0Ao Hua1Shiyou Li2Zhijie Zhang3Xiang Chen4Qiang Wang5Xing Wang6Zhiqin Chu7Xiangliang Yang8Zifu Li9Department of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Electrical and Electronic Engineering The University of Hong Kong Hong Kong P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaDepartment of Nanomedicine and Biopharmaceuticals College of Life Science and Technology Huazhong University of Science and Technology Wuhan P. R. ChinaABSTRACT An extracellular acidic environment and an intracellular mildly alkaline environment induced by carbonic anhydrase 9 (CA9) play a critical role in self‐renewal, invasion, migration, and drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report an antitumor strategy leveraging hyperbaric oxygen therapy (HBO) to regulate tumor pH and boost hydroxyethyl starch‐doxorubicin‐copper nanoparticles (HHD‐Cu NPs) against CSCs. HBO overcomes tumor hypoxia, downregulates pH‐regulatory proteins such as CA9, and leads to intracellular accumulation of acidic metabolites. As a result, HBO promotes intracellular acidification of both tumor cells and CSCs, triggering efficient doxorubicin release and the potent copper‐mediated chemical dynamic effect of subsequently administered dual‐acid‐responsive HHD‐Cu NPs. The combination of HBO with HHD‐Cu NPs not only eliminates tumor cells but also inhibits CSCs, altogether leading to potent tumor inhibition. This study explores a new function of clinical‐widely used HBO and establishes a novel combination therapy for treating CSCs abundant hypoxic solid tumors.https://doi.org/10.1002/EXP.20240080cancer stem cellscarbonic anhydrase 9hyperbaric oxygennanomedicinetumor pH |
| spellingShingle | Qingyuan Deng Ao Hua Shiyou Li Zhijie Zhang Xiang Chen Qiang Wang Xing Wang Zhiqin Chu Xiangliang Yang Zifu Li Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells Exploration cancer stem cells carbonic anhydrase 9 hyperbaric oxygen nanomedicine tumor pH |
| title | Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells |
| title_full | Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells |
| title_fullStr | Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells |
| title_full_unstemmed | Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells |
| title_short | Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells |
| title_sort | hyperbaric oxygen regulates tumor ph to boost copper doped hydroxyethyl starch conjugate nanoparticles against cancer stem cells |
| topic | cancer stem cells carbonic anhydrase 9 hyperbaric oxygen nanomedicine tumor pH |
| url | https://doi.org/10.1002/EXP.20240080 |
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