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

doi:10.1021/acs.nanolett.9b00021

	Reprogramming Tumor Immune Microenvironment (TIME) and Metabolism via Biomimetic Targeting Codelivery of Shikonin/JQ1
	Wang, Hairui 1,2; Tang, Yisi 1,2; Fang, Yuefei 1,2; Zhang, Meng 2,3; Wang, Huiyuan 2; He, Zhidi 2,3; Wang, Bing 2; Xu, Qin 1; Huang, Yongzhuo 2
刊名	NANO LETTERS
	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
DOI	10.1021/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.
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关键词	IMMUNOGENIC CELL-DEATH ; BROMODOMAIN INHIBITION ; LACTIC-ACID ; CANCER ; MACROPHAGES ; DELIVERY ; THERAPY ; BET
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000467781900022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289760]
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.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.