Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism
Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resis...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2024-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0335 |
| _version_ | 1797265643332960256 |
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| author | Chen Xiao Jiayuan Li Ao Hua Xing Wang Shiyou Li Zheng Li Chen Xu Zhijie Zhang Xiangliang Yang Zifu Li |
| author_facet | Chen Xiao Jiayuan Li Ao Hua Xing Wang Shiyou Li Zheng Li Chen Xu Zhijie Zhang Xiangliang Yang Zifu Li |
| author_sort | Chen Xiao |
| collection | DOAJ |
| description | Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients. |
| first_indexed | 2024-04-25T00:48:03Z |
| format | Article |
| id | doaj.art-ffbcfabb5d9e40569a452aa7ce30fbbc |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-04-25T00:48:03Z |
| publishDate | 2024-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-ffbcfabb5d9e40569a452aa7ce30fbbc2024-03-12T02:46:17ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742024-01-01710.34133/research.0335Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell MetabolismChen Xiao0Jiayuan Li1Ao Hua2Xing Wang3Shiyou Li4Zheng Li5Chen Xu6Zhijie Zhang7Xiangliang Yang8Zifu Li9Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.https://spj.science.org/doi/10.34133/research.0335 |
| spellingShingle | Chen Xiao Jiayuan Li Ao Hua Xing Wang Shiyou Li Zheng Li Chen Xu Zhijie Zhang Xiangliang Yang Zifu Li Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism Research |
| title | Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism |
| title_full | Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism |
| title_fullStr | Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism |
| title_full_unstemmed | Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism |
| title_short | Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism |
| title_sort | hyperbaric oxygen boosts antitumor efficacy of copper diethyldithiocarbamate nanoparticles against pancreatic ductal adenocarcinoma by regulating cancer stem cell metabolism |
| url | https://spj.science.org/doi/10.34133/research.0335 |
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