4T1 cell membrane-derived biodegradable nanosystem for comprehensive interruption of cancer cell metabolism  

作　　者：Yingzi Ren Huaqing Jing Yue Zhou Chuchu Ren Guangxu Xiao Siyu Wang Xiaoyang Liang Yunsheng Dou Ziqiao Ding Yan Zhu Xinxing Wang Nan Li 

机构地区：[1]Tianjin Key Laboratory of Drug Delivery&High-Efficiency,School of Pharmaceutical Science and Technology,Tianjin University,Tianjin 300072,China [2]Tianjin Institute of Environmental and Operational Medicine,Tianjin 300050,China [3]State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China

出　　处：《Chinese Chemical Letters》2023年第9期210-218,共9页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.82273873,31971106,81372124);National Key Research and Development Program of China(Nos.2020YFC1512304,2020YFC1512301);the Applied Basic Research Project of Tianjin(No.21JCYBJC00660);the Young Elite Scientists Sponsorship Program by Tianjin(No.0701320001);the Major Special Projects of Tianjin(No.0402080005)。

摘　　要：Glycolysis inhibition can effectively block the energy supply and interrupt tumorigenesis in many types of cancers.However,when glycolysis is inhibited,tumor cells will break down glutamine as the raw material for the replenishment pathway to maintain the tricarboxylic acid cycle ensuring energy supply,therefore inducing ineffective interruption of metabolic.Herein,we designed glutamine transporter antagonist L-γ-glutamyl-p-nitroanilide(GPNA)loaded and 4T1 cancer cell membrane coated iridium oxide nanoparticles(IrO_(2)-GPNA@CCM)to realize a comprehensive inhibition of tumor energy supply which synergistically mediated by glycolysis and glutamine cycle.IrO_(2)NPs were used to catalyze the O_(2)generation by facilitating the decomposition of endogenous H_(2)O_(2)in tumor cells,which further downregulated the expression of HIF-1αand PI3K/pAKT to interrupt the generation of lactate.Meanwhile,the loaded GPNA was released under NIR irradiation to bind to alanine-serine-cysteine transporter(ASCT2)for glutamine uptake suppression,therefore realizing the comprehensive dysfunction of cell metabolism.Moreover,both in vitro and in vivo results convinced the thorough energy inhibition effect based on Ir O_(2)-GPNA@CCM NPs,which provided an inspiring strategy for future construction of tumor therapeutic regimen.

关 键 词：Iridium oxide Glycolysis inhibition Glutamine suppression GPNA Tumor cell membrane 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R730[医药卫生—肿瘤]