Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism
Chen Xiao,
Jiayuan Li,
Ao Hua,
Xing Wang,
Shiyou Li,
Zheng Li,
Chen Xu,
Zhijie Zhang,
Xiangliang Yang,
Zifu Li
Affiliations
Chen Xiao
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Jiayuan Li
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Ao Hua
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Xing Wang
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Shiyou Li
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Zheng Li
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Chen Xu
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Zhijie Zhang
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Xiangliang Yang
Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology,
Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Zifu Li
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.
