Gemcitabine nano-prodrug reprograms intratumoral metabolism and alleviates immunosuppression for hepatocellular carcinoma therapy

被引：10

作者：

Wang, Yuehua ^{[3
,4
]}

Zhang, Bingchen ^{[5
]}

Xi, Qiye ^{[1
,2
]}

Chen, Chaojie ^{[3
]}

Wang, Zhenjie ^{[1
,2
]}

Li, Fangzhou ^{[6
]}

Wang, Shengtao ^{[1
,2
]}

Yang, Wei ^{[3
]}

Liang, Xing-Jie ^{[6
,7
]}

Yu, Zhiqiang ^{[1
,2
,5
]}

Yu, Meng ^{[1
,2
,8
]}

机构：

[1] Southern Med Univ, Sch Pharmaceut Sci, NMPA Key Lab Res & Evaluat Drug Metab, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China

[3] Univ Shanghai Sci & Technol, Shidong Hosp, Base Achievement Transformat, Shanghai 200438, Peoples R China

[4] Univ Shanghai Sci & Technol, Sch Hlth Sci & Engn, Shanghai 200093, Peoples R China

[5] Southern Med Univ, Affiliated Dongguan Hosp, Dongguan Inst Clin Canc Res, Dept Lab Med, Dongguan 523018, Peoples R China

[6] Natl Ctr Nanosci & Technol China, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 First North Rd, Beijing 100190, Peoples R China

[7] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[8] Southern Med Univ, Zhujiang Hosp, Guangzhou 510282, Peoples R China

来源：

NANO TODAY | 2023年 / 53卷

基金：

中国国家自然科学基金;

关键词：

Gemcitabine; Glycolysis metabolism; Glutamine metabolism; Immunotherapy; Hepatocellular carcinoma; CANCER; TUMOR; TRANSPORT; CELLS;

D O I：

10.1016/j.nantod.2023.102009

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

High-rate aerobic glycolysis and abnormal glutamine metabolism in tumor cells lead to their unlimited malignant proliferation and induce immune escape in the tumor microenvironment. In this study, the GLS1 inhibitor BPTES and the PDHC inhibitor CPI-613 were co-delivered by an ROS-sensitive GEM nano-prodrug (PD-G@BC), and a simultaneous inhibition of glycolysis and glutamine metabolism was achieved to deprive tumor cells of nutrient supply. In addition, this metabolism reprogramming effectively weakened the sources of glucose and glutamine in tumor cells, correspondingly thrived metabolism in antitumor immune cells, thereby increasing the intratumoral infiltration and functions of the immunogenic cells to alleviate the immunosuppressive responses. This multifunctional combination strategy will provide new insights into the design of synergistic cancer immunotherapy based on metabolic interventions.

引用

页数：16

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