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Gemcitabine-loaded synthetic high-density lipoprotein preferentially eradicates hepatic monocyte-derived macrophages in mouse liver with colorectal cancer metastases

文献类型：期刊论文

作者Xiong, Feng-qin2,3,4; Zhang, Wen2,3,4; Zheng, Chao2,3,4; Li, Yu7; Gong, Xiang2,3,4; Zhang, Yuan5; Wang, Hao2; Zhang, Peng-cheng3,4,6; Li, Ya-ping1,3,4,7
刊名ACTA PHARMACOLOGICA SINICA
出版日期2023-05-24
页码11
ISSN号1671-4083
关键词colorectal cancer liver metastasis synthetic high-density lipoprotein gemcitabine macrophages
DOI10.1038/s41401-023-01110-w
通讯作者Wang, Hao(wanghao@sphchina.com) ; Zhang, Peng-cheng(zhangpch1@shanghaitech.edu.cn) ; Li, Ya-ping(ypli@simm.ac.cn)
英文摘要Liver metastasis of colorectal cancer (CRC) is the critical cause of CRC-related death due to its unique immunosuppressive microenvironment. In this study we generated a gemcitabine-loaded synthetic high-density lipoprotein (G-sHDL) to reverse immunosuppression in livers with CRC metastases. After intravenous injection, sHDL targeted hepatic monocyte-derived alternatively activated macrophages (Mono-M2) in the livers of mice bearing both subcutaneous tumors and liver metastases. The G-sHDL preferentially eradicated Mono-M2 in the livers with CRC metastases, which consequently prevented Mono-M2-mediated killing of tumor antigen-specific CD8(+) T cells in the livers and thus improved the densities of tumor antigen-specific CD8(+) T cells in the blood, tumor-draining lymph nodes and subcutaneous tumors of the treated mice. While reversing the immunosuppressive microenvironment, G-sHDL also induced immunogenic cell death of cancer cells, promoted maturation of dendritic cells, and increased tumor infiltration and activity of CD8(+) T cells. Collectively, G-sHDL inhibited the growth of both subcutaneous tumors and liver metastases, and prolonged the survival of animals, which could be further improved when used in conjunction with anti-PD-L1 antibody. This platform can be a generalizable platform to modulate immune microenvironment of diseased livers.
WOS关键词1ST-LINE TREATMENT ; DRUG-DELIVERY ; FLUOROURACIL ; IMMUNOTHERAPY ; NANOPARTICLES ; OXALIPLATIN ; APOPTOSIS ; EFFICACY ; CELLS
资助项目National Natural Science Foundation of China[32171374] ; National Natural Science Foundation of China[82270064] ; National Natural Science Foundation of China[31870995] ; Shandong Provincial Natural Science Foundation[ZR2019ZD25]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:000994507100002
源URL[http://119.78.100.183/handle/2S10ELR8/306179]  
专题新药研究国家重点实验室
通讯作者Wang, Hao; Zhang, Peng-cheng; Li, Ya-ping
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Yantai 264000, Peoples R China
2.China State Inst Pharmaceut Ind, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
5.Tongji Univ, Shanghai Pulm Hosp, Dept Pulm & Crit Care Med, Sch Med, Shanghai 200433, Peoples R China
6.ShanghaiTech Univ, Sch Biomed Engn, Shanghai 201210, Peoples R China
7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Xiong, Feng-qin,Zhang, Wen,Zheng, Chao,et al. Gemcitabine-loaded synthetic high-density lipoprotein preferentially eradicates hepatic monocyte-derived macrophages in mouse liver with colorectal cancer metastases[J]. ACTA PHARMACOLOGICA SINICA,2023:11.
APA Xiong, Feng-qin.,Zhang, Wen.,Zheng, Chao.,Li, Yu.,Gong, Xiang.,...&Li, Ya-ping.(2023).Gemcitabine-loaded synthetic high-density lipoprotein preferentially eradicates hepatic monocyte-derived macrophages in mouse liver with colorectal cancer metastases.ACTA PHARMACOLOGICA SINICA,11.
MLA Xiong, Feng-qin,et al."Gemcitabine-loaded synthetic high-density lipoprotein preferentially eradicates hepatic monocyte-derived macrophages in mouse liver with colorectal cancer metastases".ACTA PHARMACOLOGICA SINICA (2023):11.

入库方式： OAI收割

来源：上海药物研究所

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