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

文献类型：期刊论文

作者Chen, Binfan3,4; Gao, Ang3; Tu, Bin3,4; Wang, Yonghui3,4; Yu, Xiaolu3,4; Wang, Yingshu1,3; Xiu, Yanfeng1; Wang, Bing3; Wan, Yakun3; Huang, Yongzhuo2,3,4,5
刊名BIOMATERIALS
出版日期2020-10-01
卷号255页码:12
ISSN号0142-9612
关键词Tumor-associated macrophage Glycolysis mTOR Angiogenesis Tumor immune microenvironment Liposome
DOI10.1016/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.
WOS关键词MACROPHAGE POLARIZATION ; MAMMALIAN TARGET ; M2 ; NORMALIZATION ; OPPORTUNITIES ; MECHANISMS ; PHENOTYPE ; RESPONSES ; DELIVERY
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研究方向Engineering ; Materials Science
语种英语
出版者ELSEVIER SCI LTD
WOS记录号WOS:000555693800028
源URL[http://119.78.100.183/handle/2S10ELR8/292259]  
专题新药研究国家重点实验室
通讯作者Huang, Yongzhuo
作者单位1.Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Zhongshan Branch, Inst Drug Res & Dev, Zhongshan, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing, 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.

入库方式： OAI收割

来源：上海药物研究所

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