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

文献类型：期刊论文

作者Wang, Junyang1,8,9; Zheng, Chao1,3,9; Zhai, Yihui1,4,9; Cai, Ying1,4,9; Lee, Robert J.5,8; Xing, Jianming8; Wang, Hao3; Zhu, Helen H.6; Teng, Lesheng8; Li, Yaping1,2,4,7,9
刊名NANO TODAY
出版日期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
DOI10.1016/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.
WOS关键词CANCER ; NANOPARTICLES ; CHOLESTEROL ; POLARIZATION ; CHEMOTHERAPY ; MECHANISMS ; DELIVERY ; THERAPY ; PROMOTE ; GROWTH
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研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000637809700006
出版者ELSEVIER SCI LTD
源URL[http://119.78.100.183/handle/2S10ELR8/296591]  
专题新药研究国家重点实验室
通讯作者Teng, Lesheng; Li, Yaping; Zhang, Pengcheng
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
2.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China
3.China State Inst Pharmaceut Ind, Shanghai 200040, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Ohio State Univ, Div Pharmaceut & Pharmaceut Chem, Coll Pharm, Columbus, OH 43210 USA
6.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
7.Yantai Univ, Sch Pharm, Yantai 264005, Shandong, Peoples R China
8.Jilin Univ, Sch Life Sci, Changchun 130012, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, 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.

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来源：上海药物研究所

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