Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism  

作　　者：Chen Xiao Jiayuan Li Ao Hua Xing Wang Shiyou Li Zheng Li Chen Xu Zhijie Zhang Xiangliang Yang Zifu Li 

机构地区：[1]Department of Nanomedicine and Biopharmaceuticals,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [2]National Engineering Research Center for Nanomedicine,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [3]Key Laboratory of Molecular Biophysics of Ministry of Education,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [4]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [5]Hubei Engineering Research Center for Biomaterials and Medical Protective Materials,Huazhong University of Science and Technology,Wuhan 430074,P.R.China [6]Hubei Bioinformatics and Molecular Imaging Key Laboratory,Huazhong University of Science and Technology,Wuhan 430074,P.R.China

出　　处：《Research》2024年第4期458-476,共19页研究(英文)

基　　金：supported by grants from the National Research and Development Program of China(2020YFA0211200,2020YFA0710700,2021YFA1201200,and 2022YFA1206000);the National Science Foundation of China(82172757 and 31972927);the Program for HUST Academic Frontier Youth Team(2018QYTD01);the HCP Program for HUST.

摘　　要：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 cuproptosisinduced 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.

关 键 词：METABOLISM OXYGEN holds 

分 类 号：R73[医药卫生—肿瘤]