High-density lipoprotein modulates tumor-associated macrophage for chemoimmunotherapy of hepatocellular carcinoma

doi:10.1016/j.nantod.2020.101064

	High-density lipoprotein modulates tumor-associated macrophage for chemoimmunotherapy of hepatocellular carcinoma
	Wang, Junyang 3,4,5; Zheng, Chao 4,5,6; Zhai, Yihui 4,5,7; Cai, Ying 4,5,7; Lee, Robert J.3,8; Xing, Jianming 3; Wang, Hao 6; Zhu, Helen H.9; Teng, Lesheng 3; Li, Yaping 1,2,4,5,7
刊名	NANO TODAY
	2021-04-01
卷号	37 页码:11
关键词	Tumor-associated macrophages High-density lipoproteins Immunotherapy Hepatocellular carcinoma Immunosuppression
ISSN号	1748-0132
DOI	10.1016/j.nantod.2020.101064
通讯作者	Teng, Lesheng(tenglesheng@jlu.edu.cn) ; Li, Yaping(ypli@simm.ac.cn) ; Zhang, Pengcheng(pzhang@simm.ac.cn)
英文摘要	Intratumoral abundance of alternatively activated macrophages (M2) in hepatocellular carcinoma (HCC) is associated with advanced stages, poor prognosis and failure of checkpoint blockade immunotherapy. In this work, we discover that synthetic high-density lipoproteins (sHDLs) preferentially deliver cargoes into M2 and Hepa1-6 HCC cells, based on which finding we create a functional sHDL containing esterase-responsive prodrugs of vadimezan and gemcitabine (VG-sHDLs). The VG-sHDLs induce the HCC cells to release damage-associated molecular patterns (high mobility group box 1 protein and ATP) and cytokines including macrophage colony stimulating factor and type I interferons, improving monocyte differentiation into classically activated macrophages (M1) and dendritic cells. Meanwhile, the VG-sHDLs kill M2 without significant toxicity to M1. After intravenous injection, the VG-sHDLs increase intratumoral M1 as well as proinflammatory molecules such as C-X-C motif ligand 9 and 10 and interleukin 12, but reduce M2 and antiinflammatory cytokine interleukin 10. These changes enhance the recruitment and activity of cytotoxic T lymphocytes, which eradicate HCC tumors and also establish tumor-specific immune memory that prevents recurrence. This work sheds light on the interactions between sHDL and intratumoral cells, and provides rationale for chemoimmunotherapy of HCC using conventional chemotherapeutics and emerging immune modulators. (C) 2021 Elsevier Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[31870995] ; National Natural Science Foundation of China[81690265] ; National Natural Science Foundation of China[81671808] ; National Natural Science Foundation of China[81630052] ; National Natural Science Foundation of China[31930066] ; Shandong Provincial Natural Science Foundation[ZR2019ZD25] ; Youth Innovation Promotion Association of CAS[2017335] ; SA-SIBS Scholarship Program
WOS关键词	CANCER ; NANOPARTICLES ; CHOLESTEROL ; POLARIZATION ; CHEMOTHERAPY ; MECHANISMS ; DELIVERY ; THERAPY ; PROMOTE ; GROWTH
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000637809700006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296591]
专题	中国科学院上海药物研究所
通讯作者	Teng, Lesheng; Li, Yaping; Zhang, Pengcheng
作者单位	1.Yantai Univ, Sch Pharm, Yantai 264005, Shandong, Peoples R China 2.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China 3.Jilin Univ, Sch Life Sci, Changchun 130012, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 6.China State Inst Pharmaceut Ind, Shanghai 200040, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 8.Ohio State Univ, Div Pharmaceut & Pharmaceut Chem, Coll Pharm, Columbus, OH 43210 USA 9.Shanghai Jiao Tong Univ, Ren Ji Hosp, Renji Med X Stem Cell Res Ctr,Dept Urol, Sch Med & Sch Biomed Engn,State Key Lab Oncogenes, Shanghai 200127, Peoples R China
推荐引用方式 GB/T 7714	Wang, Junyang,Zheng, Chao,Zhai, Yihui,et al. High-density lipoprotein modulates tumor-associated macrophage for chemoimmunotherapy of hepatocellular carcinoma[J]. NANO TODAY,2021,37:11.
APA	Wang, Junyang.,Zheng, Chao.,Zhai, Yihui.,Cai, Ying.,Lee, Robert J..,...&Zhang, Pengcheng.(2021).High-density lipoprotein modulates tumor-associated macrophage for chemoimmunotherapy of hepatocellular carcinoma.NANO TODAY,37,11.
MLA	Wang, Junyang,et al."High-density lipoprotein modulates tumor-associated macrophage for chemoimmunotherapy of hepatocellular carcinoma".NANO TODAY 37(2021):11.