Citation: Yingzi Ren, Huaqing Jing, Yue Zhou, Chuchu Ren, Guangxu Xiao, Siyu Wang, Xiaoyang Liang, Yunsheng Dou, Ziqiao Ding, Yan Zhu, Xinxing Wang, Nan Li. 4T1 cell membrane-derived biodegradable nanosystem for comprehensive interruption of cancer cell metabolism[J]. Chinese Chemical Letters, ;2023, 34(9): 108161. doi: 10.1016/j.cclet.2023.108161 shu

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

Yingzi Ren ^a ,
Huaqing Jing ^a ,
Yue Zhou ^a ,
Chuchu Ren ^a ,
Guangxu Xiao ^c ,
Siyu Wang ^a ,
Xiaoyang Liang ^a ,
Yunsheng Dou ^a ,
Ziqiao Ding ^a ,
Yan Zhu ^c ,
Xinxing Wang ^{b, *,} ,
Nan Li ^{a, *,}

a.
Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
b.
Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China
c.
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

wxxemail@sina.cn

linan1985@tju.edu.cn

Received Date: 20 October 2022
Revised Date: 19 January 2023
Accepted Date: 26 January 2023
Available Online: 28 January 2023

Figures(4)

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 (IrO₂-GPNA@CCM) to realize a comprehensive inhibition of tumor energy supply which synergistically mediated by glycolysis and glutamine cycle. IrO₂ NPs were used to catalyze the O₂ generation by facilitating the decomposition of endogenous H₂O₂ in tumor cells, which further downregulated the expression of HIF-1α and 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 IrO₂-GPNA@CCM NPs, which provided an inspiring strategy for future construction of tumor therapeutic regimen.
- Iridium oxide,
- Glycolysis inhibition,
- Glutamine suppression,
- GPNA,
- Tumor cell membrane
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