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Anti-alcoholism drug disulfiram for targeting glioma energy metabolism using BBB-penetrating delivery of fixed-dose combination

文献类型：期刊论文

作者Zhao, Pengfei2,3,4,5; Qu, Jingkun2,3; Wu, Aihua6; Wang, Shuang3; Tang, Xueping3,7; Ou, Ante3; Zhang, Jiaxin3; Xu, Yi8; Zhao, Qiang1,2,3,4; Huang, Yongzhuo2,3,4,9,10
刊名NANO TODAY
出版日期2022-06-01
卷号44页码:16
关键词Fixed-dose codelivery Glioma Energy metabolism Tumor immune microenvironment Disulfiram Shikonin Immunogenic cell death Tumor-associated macrophage
ISSN号1748-0132
DOI10.1016/j.nantod.2022.101448
通讯作者Zhao, Qiang(zhaoq@simm.ac.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要The interconnection between tumor metabolism and the immune microenvironment governs the progression of glioma. It was revealed that the metabolic enzymes ALDH1L1 and PKM2 were overexpressed in glioma. We discovered that the anti-alcoholism drug disulfiram (DSF) can intervene in the tumor energy metabolism by inhibiting ATP supply via an alternative pathway, of which ALDH1L1 is an essential enzyme in the 10-formyl-tetrahydrofolate-NADH-ATP metabolism axis. We thus proposed a dual-inhibition strategy by using a combination therapy of a PKM2 inhibitor shikonin (SHK) and an ALDH1L1 inhibitor DSF. By simultaneously inhibiting glycolysis and NADH-ATP metabolism, the ATP generation in the tumor cells can be efficiently cut down. A BBB-penetrating hybrid albumin/lactoferrin nanosystem (termed BSA/LF NP) was developed for biomimetic codelivery of DSF/SHK for anti-glioma therapy. Due to the overexpression of SPARC and LRP-1 in both the BBB and glioma cells, the BSA/LF NP could efficiently enter the glioma. More importantly, it can deliver a fixed-dose ratio of DSF and SHK to the glioma, providing a basis for synergistic effect in combination therapy. The BSA/LF NP effectively prolonged the survival of glioma mice by interactive modulation of energy metabolism (via both glycolysis and NADH-ATP pathways) and immune microenvironment. The work provided a promising glioma-targeting strategy for a fixed-dose combination and a potent ATP-depletion treatment.0 2022 Published by Elsevier Ltd.
WOS关键词TUMOR MICROENVIRONMENT ; CANCER ; MACROPHAGES ; SHIKONIN ; SERINE ; TRANSCYTOSIS ; MAINTENANCE ; GLYCOLYSIS ; EXPRESSION ; RECEPTORS
资助项目National Key Research and Development Program of China, China[2021YFE0103100] ; National Key Research and Development Program of China, China[2021YFC2400600] ; NFSC[81925035] ; NFSC[81521005] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai SciTech Innovation Initiative[18430740800]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000788719500001
出版者ELSEVIER SCI LTD
源URL[http://119.78.100.183/handle/2S10ELR8/299304]  
专题新药研究国家重点实验室
通讯作者Zhao, Qiang; Huang, Yongzhuo
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210023, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, SIMM, Zhongshan 528437, Peoples R China
5.Zhejiang Univ, Ctr Clin Pharmacol, Affiliated Hosp 2, Sch Med, 88 Jiefang Rd, Hangzhou 310009, Peoples R China
6.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, 826 Zhangheng Rd, Shanghai 201203, Peoples R China
7.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, 12 Jichang Rd, Guangzhou 510405, Peoples R China
8.Ningbo First Hosp, Dept Cardiol, 59 Liuting St, Ningbo 315010, Peoples R China
9.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhao, Pengfei,Qu, Jingkun,Wu, Aihua,et al. Anti-alcoholism drug disulfiram for targeting glioma energy metabolism using BBB-penetrating delivery of fixed-dose combination[J]. NANO TODAY,2022,44:16.
APA Zhao, Pengfei.,Qu, Jingkun.,Wu, Aihua.,Wang, Shuang.,Tang, Xueping.,...&Huang, Yongzhuo.(2022).Anti-alcoholism drug disulfiram for targeting glioma energy metabolism using BBB-penetrating delivery of fixed-dose combination.NANO TODAY,44,16.
MLA Zhao, Pengfei,et al."Anti-alcoholism drug disulfiram for targeting glioma energy metabolism using BBB-penetrating delivery of fixed-dose combination".NANO TODAY 44(2022):16.

入库方式： OAI收割

来源：上海药物研究所

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