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Remodeling tumor immune microenvironment (TIME) for glioma therapy using multi-targeting liposomal codelivery

文献类型：期刊论文

作者Zheng, Zening1,2; Zhang, Jiaxin2,3; Jiang, Jizong2; He, Yang2; Zhang, Wenyuan2; Mo, Xiaopeng2; Kang, Xuejia2; Xu, Qin1; Wang, Bing2; Huang, Yongzhuo2,4,5
刊名JOURNAL FOR IMMUNOTHERAPY OF CANCER
出版日期2020
卷号8期号:2页码:16
关键词tumor microenvironment macrophages brain neoplasms immunotherapy
DOI10.1136/jitc-2019-000207
通讯作者Xu, Qin(xuqin@gzucm.edu.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要Background Glioblastoma (GBM) treatment is undermined by the suppressive tumor immune microenvironment (TIME). Seek for effective methods for brain TIME modulation is a pressing need. However, there are two major challenges against achieving the goal: first, to screen the effective drugs with TIME-remodeling functions and, second, to develop a brain targeting system for delivering the drugs. Methods In this study, an alpha 7 nicotinic acetylcholine receptors (nAChRs)-binding peptide(D)CDX was used to modify the codelivery liposomes to achieve a 'three-birds-one-stone' delivery strategy, that is, multi-targeting the glioma vessel endothelium, glioma cells, and tumor-associated macrophages that all overexpressed alpha 7 nAChRs. A brain-targeted liposomal honokiol and disulfiram/copper codelivery system (CDX-LIPO) was developed for combination therapy via regulating mTOR (mammalian target of rapamycin) pathway for remodeling tumor metabolism and TIME. Honokiol can yield a synergistic effect with disulfiram/copper for anti-GBM. Results It was demonstrated that CDX-LIPO remarkably triggered tumor cell autophagy and induced immunogenic cell death, and meanwhile, activated the tumor-infiltrating macrophage and dendritic cells, and primed T and NK (natural killer) cells, resulting in antitumor immunity and tumor regression. Moreover, CDX-LIPO promoted M1-macrophage polarization and facilitated mTOR-mediated reprogramming of glucose metabolism in glioma. Conclusion This study developed a potential combinatory therapeutic strategy by regulation of TIME and a 'three-birds-one-stone'-like glioma-targeting drug delivery system.
WOS关键词NONNEURONAL CHOLINERGIC SYSTEM ; ACETYLCHOLINE-RECEPTORS ; CANCER ; AUTOPHAGY ; BRAIN ; PATHWAY ; GLIOBLASTOMA ; MACROPHAGES ; DISULFIRAM ; METABOLISM
资助项目NFSC[81925035] ; NFSC[81673382] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018Zx09711002-010-002] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai SciTech Innovation Initiative[18430740800] ; Fudan-SIMM Joint Research Fund[FU-SIMM20174009]
WOS研究方向Oncology ; Immunology
语种英语
WOS记录号WOS:000564352500006
出版者BMJ PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/291577]  
专题新药研究国家重点实验室
通讯作者Xu, Qin; Huang, Yongzhuo
作者单位1.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China
4.NMPA Key Lab Qual Res & Evaluat PharmaceuticalExc, Shanghai, Peoples R China
5.ChineseAcad Sci, Zhongshan Branch, Inst Drug Res & Dev, Zhongshan, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Zening,Zhang, Jiaxin,Jiang, Jizong,et al. Remodeling tumor immune microenvironment (TIME) for glioma therapy using multi-targeting liposomal codelivery[J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER,2020,8(2):16.
APA Zheng, Zening.,Zhang, Jiaxin.,Jiang, Jizong.,He, Yang.,Zhang, Wenyuan.,...&Huang, Yongzhuo.(2020).Remodeling tumor immune microenvironment (TIME) for glioma therapy using multi-targeting liposomal codelivery.JOURNAL FOR IMMUNOTHERAPY OF CANCER,8(2),16.
MLA Zheng, Zening,et al."Remodeling tumor immune microenvironment (TIME) for glioma therapy using multi-targeting liposomal codelivery".JOURNAL FOR IMMUNOTHERAPY OF CANCER 8.2(2020):16.

入库方式： OAI收割

来源：上海药物研究所

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