Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy

作     者：Guofeng Ji Lushun Ma Haochen Yao Sheng Ma Xinghui Si Yalin Wang Xin Bao Lili Ma Fangfang Chen Chong Ma Leaf Huang Xuedong Fang Wantong Song Guofeng Ji;Lushun Ma;Haochen Yao;Sheng Ma;Xinghui Si;Yalin Wang;Xin Bao;Lili Ma;Fangfang Chen;Chong Ma;Leaf Huang;Xuedong Fang;Wantong Song

作者机构：Department of Gastrointestinal and Colorectal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Division of Pharmacoengineering and Molecular PharmaceuticsEshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillNC 27599USA Key Laboratory of ZoonosisChinese Ministry of EducationCollege of Basic Medical ScienceJilin UniversityChangchun 130021China Second Hospital of Shandong UniversityJinan 250000China Second Hospital of Jilin UniversityChangchun 130041China Jilin Biomedical Polymers Engineering LaboratoryChangchun 130022China State Key Laboratory of Inorganic Synthesis and Preparative ChemistryCollege of ChemistryJilin UniversityChangchun 130012China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2020年第10卷第11期

页      面：2171-2182页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：financially supported by the National Natural Science Foundation of China(51673189,51973215,51833010and 51520105004) Ministry of Science and Technology of China(Project 2018ZX09711003-012) the Program of Scientific Development of Jilin Province(20170101100JC,20180520207JH,20190103112JH,China) supported by NIH grant CA198999(USA) 

主　　题：Obeticholic acid Farnesoid X receptor Nanoemulsion Liver sinusoidal endothelial cells Liver cancer 

摘      要：Primary bile acids were reported to augment secretion of chemokine(C-X-C motif)ligand16(CXCL16)from liver sinusoidal endothelial cells(LSECs)and trigger natural killer T(NKT)cellbased immunotherapy for liver ***,abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer *** advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation,we proposed a strategy using nanoemulsion-loaded obeticholic acid(OCA),a clinically approved selective farnesoid X receptor(FXR)agonist,for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer *** OCA-nanoemulsion(OCA-NE)was prepared via ultrasonic emulsification method,with a diameter of 184 nm and good *** vivo biodistribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer *** a result,OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model,which performed much better than oral medication of free *** analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-g,as well as increased NKT cell populations inside the ***,our research provides a new evidence for the antitumor effect of receptors for primary bile acids,and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy.