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Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer

文献类型：期刊论文

作者Zheng, Chao6,7,8; Zhang, Wen6,7,8; Wang, Jinming3,4; Zhai, Yihui2,6,7; Xiong, Fengqin6,7,8; Cai, Ying2,6,7; Gong, Xiang6,7,8; Zhu, Binyu2,6,7; Zhu, Helen He3,4; Wang, Hao8
刊名ACTA PHARMACEUTICA SINICA B
出版日期2022-09-01
卷号12期号:9页码:3726-3738
ISSN号2211-3835
关键词KEY WORDS High-density lipoprotein Immunotherapy Combination therapy Metastasis Triple-negative breast cancer Lenvatinib Vadimezan Immune checkpoint blockade
DOI10.1016/j.apsb.2022.02.021
通讯作者Wang, Hao(wanghao99@hotmail.com) ; Li, Yaping(ypli@simm.ac.cn) ; Zhang, Pengcheng(pzhang@simm.ac.cn)
英文摘要Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33-and 13-fold, respec-tively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and pro-longed the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combina-tion use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.(c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
WOS关键词DRUG-DELIVERY ; I INTERFERONS ; IMMUNOTHERAPY ; CHEMOTHERAPY ; IMMUNITY ; RECEPTOR
资助项目National Natural Science Foundation of China[32171374] ; National Natural Science Foundation of China[31870995] ; National Natural Science Foundation of China[81671808] ; Shandong Provincial Natural Science Foundation, China[ZR2019ZD25]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号WOS:000865010500003
源URL[http://119.78.100.183/handle/2S10ELR8/303259]  
专题新药研究国家重点实验室
通讯作者Wang, Hao; Li, Yaping; Zhang, Pengcheng
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Yantai 264000, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200135, Peoples R China
4.Shanghai Jiao Tong Univ, Ren Ji Hosp, Renji Medx Stem Cell Res Ctr, Sch Med,Dept Urol,State Key Lab Oncogenes & Relate, Shanghai 200135, Peoples R China
5.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
8.China State Inst Pharmaceut Ind, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Chao,Zhang, Wen,Wang, Jinming,et al. Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer[J]. ACTA PHARMACEUTICA SINICA B,2022,12(9):3726-3738.
APA Zheng, Chao.,Zhang, Wen.,Wang, Jinming.,Zhai, Yihui.,Xiong, Fengqin.,...&Zhang, Pengcheng.(2022).Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer.ACTA PHARMACEUTICA SINICA B,12(9),3726-3738.
MLA Zheng, Chao,et al."Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer".ACTA PHARMACEUTICA SINICA B 12.9(2022):3726-3738.

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来源：上海药物研究所

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