Metabolic modulation via mTOR pathway and anti-angiogenesis remodels tumor microenvironment using PD-L1-targeting codelivery

doi:10.1016/j.biomaterials.2020.120187

	Metabolic modulation via mTOR pathway and anti-angiogenesis remodels tumor microenvironment using PD-L1-targeting codelivery
	Chen, Binfan 1,2; Gao, Ang 1; Tu, Bin 1,2; Wang, Yonghui 1,2; Yu, Xiaolu 1,2; Wang, Yingshu 1,3; Xiu, Yanfeng 3; Wang, Bing 1; Wan, Yakun 1; Huang, Yongzhuo 1,2,4,5
刊名	BIOMATERIALS
	2020-10-01
卷号	255 页码:12
关键词	Tumor-associated macrophage Glycolysis mTOR Angiogenesis Tumor immune microenvironment Liposome
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2020.120187
通讯作者	Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要	Tumor microenvironment (TME) closely affects cancer progression by promoting cancer cell survival and proliferation, drug resistance, metastasis, and immunosuppression as well. Remodeling TME is a promising therapeutic strategy for anticancer. mTOR signaling is an essential regulator for cellular metabolism and tumor-associated macrophages (TAMs) repolarization. There is an integrated crosstalk among mTOR/metabolism/ immunity. Angiogenesis can also regulate metabolism and immunity. Based on these, a potential therapeutic avenue was developed by targeting mTOR and angiogenesis to remodel tumor immune microenvironment (TIME). A dual-targeting delivery liposomal system was designed with dual-modification of PD-L1 nanobody and mannose ligands for co-delivering an mTOR inhibitor (rapamycin) and an anti-angiogenic drug (regorafenib). The liposomes were able to target both TAMs and cancer cells that overexpressed PD-L1 and mannose receptors. The liposomes efficiently reduced glycolysis, repolarized TAMs, inhibited angiogenesis, reprogrammed immune cells, and consequently arrested tumor growth.
资助项目	National Natural Science Foundation of China[NSFC 81925035] ; National Natural Science Foundation of China[81673382] ; National Natural Science Foundation of China[81521005] ; Strategic Priority Research Program of CAS, China[XDA12050307] ; National Special Project for Significant New Drugs Development, China[2018ZX09711002-010-002] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai SciTech Innovation Initiative[18430740800] ; FudanSIMM Joint Research Fund, China[FU-SIMM20174009]
WOS关键词	MACROPHAGE POLARIZATION ; MAMMALIAN TARGET ; M2 ; NORMALIZATION ; OPPORTUNITIES ; MECHANISMS ; PHENOTYPE ; RESPONSES ; DELIVERY
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000555693800028
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292259]
专题	中国科学院上海药物研究所
通讯作者	Huang, Yongzhuo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China 4.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing, Peoples R China 5.Chinese Acad Sci, Zhongshan Branch, Inst Drug Res & Dev, Zhongshan, Peoples R China
推荐引用方式 GB/T 7714	Chen, Binfan,Gao, Ang,Tu, Bin,et al. Metabolic modulation via mTOR pathway and anti-angiogenesis remodels tumor microenvironment using PD-L1-targeting codelivery[J]. BIOMATERIALS,2020,255:12.
APA	Chen, Binfan.,Gao, Ang.,Tu, Bin.,Wang, Yonghui.,Yu, Xiaolu.,...&Huang, Yongzhuo.(2020).Metabolic modulation via mTOR pathway and anti-angiogenesis remodels tumor microenvironment using PD-L1-targeting codelivery.BIOMATERIALS,255,12.
MLA	Chen, Binfan,et al."Metabolic modulation via mTOR pathway and anti-angiogenesis remodels tumor microenvironment using PD-L1-targeting codelivery".BIOMATERIALS 255(2020):12.