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Reprogramming Tumor Immune Microenvironment (TIME) and Metabolism via Biomimetic Targeting Codelivery of Shikonin/JQ1

文献类型：期刊论文

作者Wang, Hairui1,2; Tang, Yisi1,2; Fang, Yuefei1,2; Zhang, Meng2,3; Wang, Huiyuan2; He, Zhidi2,3; Wang, Bing2; Xu, Qin1; Huang, Yongzhuo2
刊名NANO LETTERS
出版日期2019-05-01
卷号19期号:5页码:2935-2944
关键词Biomimetic delivery glucose metabolism immunogenic cell death (ICD) tumor-associated macrophage shikonin JQ1
ISSN号1530-6984
DOI10.1021/acs.nanolett.9b00021
通讯作者Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要Remodeling tumor immune microenvironment (TIME) is an important strategy to lift the immunosuppression and achieve immune normalization. In this work a mannosylated lactoferrin nanoparticulate system (Man-LF NPs) is developed for dual-targeting biomimetic codelivery of shikonin and JQ1 via the mannose receptor and LRP-1 that are overexpressed in both cancer cells and tumor-associated macrophages. The Man-LF NPs can serve as multitarget therapy for inducing immune cell death in the cancer cells, repressing glucose metabolism and repolarizing tumor-associated macrophages, and consequently, lead to remodeling the TIME (e.g., promotion of dendritic cell maturation and CD8(+) T cell infiltration, as well as suppression of Treg). Moreover, JQ1 is a suppressor of PD-L1, and the Man-LF NPs can also work on PD-L1 checkpoint blockage. The results reveal the synergistic combination of shikonin and JQ1 and the treatment potency of the Man-LF NPs. Importantly, it is demonstrated that the interaction between the tumor metabolism and immunity plays an essential role in immunotherapy, and the developed drug combination and nanoformulation can target the multiple components in the complicated network of TIME, providing a potential therapeutic strategy.
WOS关键词IMMUNOGENIC CELL-DEATH ; BROMODOMAIN INHIBITION ; LACTIC-ACID ; CANCER ; MACROPHAGES ; DELIVERY ; THERAPY ; BET
资助项目NFSC[814022883] ; NFSC[81422048] ; NFSC[81673382] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; CAS Scientific Research and Equipment Development Project[YZ201437] ; Fudan-SIMM Joint Research Fund[FU-SIMM20174009]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
WOS记录号WOS:000467781900022
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/289760]  
专题新药研究国家重点实验室
通讯作者Huang, Yongzhuo
作者单位1.Guangzhou Univ Chinese Med, Inst Trop Med, 12 Jichang Rd, Guangzhou 510450, Guangdong, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Hairui,Tang, Yisi,Fang, Yuefei,et al. Reprogramming Tumor Immune Microenvironment (TIME) and Metabolism via Biomimetic Targeting Codelivery of Shikonin/JQ1[J]. NANO LETTERS,2019,19(5):2935-2944.
APA Wang, Hairui.,Tang, Yisi.,Fang, Yuefei.,Zhang, Meng.,Wang, Huiyuan.,...&Huang, Yongzhuo.(2019).Reprogramming Tumor Immune Microenvironment (TIME) and Metabolism via Biomimetic Targeting Codelivery of Shikonin/JQ1.NANO LETTERS,19(5),2935-2944.
MLA Wang, Hairui,et al."Reprogramming Tumor Immune Microenvironment (TIME) and Metabolism via Biomimetic Targeting Codelivery of Shikonin/JQ1".NANO LETTERS 19.5(2019):2935-2944.

入库方式： OAI收割

来源：上海药物研究所

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