文献类型：期刊文献

英文题名：Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity

作者：Ji, Keqin[1];Fan, Mingrui[1];Huang, Dong[1];Sun, Lingna[1];Li, Bingqin[1];Xu, Ruoting[1];Zhang, Jiajing[1];Shao, Xuan[1];Chen, Yanzuo[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Shanghai Key Lab New Drug Design,Minist Educ, Shanghai 200237, Peoples R China

年份：2022

卷号：10

期号：3

起止页码：702

外文期刊名：BIOMATERIALS SCIENCE

收录：;EI(收录号：20220711616460);WOS:【SCI-EXPANDED(收录号:WOS:000731673400001)】；

基金：This work was supported by the Natural Science Foundation of Shanghai (no. 19ZR1472500, China).

语种：英文

外文关键词：Antigen-antibody reactions - Cell culture - Controlled drug delivery - Liver - Macrophages - Targeted drug delivery

摘要：Liver fibrosis therapy remains limited due to the inefficiency of drug delivery and inflammation induced by Kupffer cells. In this study, an exosome-liposome hybrid drug delivery system (LIEV) was developed to increase the efficacy of clodronate (CLD)-inhibition of Kupffer cells and to effectively deliver nintedanib (NIN) to liver fibroblasts to ensure enhanced anti-fibrosis therapy. CLD and NIN co-loaded LIEV (CLD/NIN@LIEV) exerted non-specific inhibition of phagocytosis by Kupffer cells, reduced inflammatory cytokines, and showed homologous homing properties mediated by fibroblast-derived exosomes, thereby achieving superior antifibrotic effects in a CCl4-induced fibrosis mouse model by inhibiting the proliferation of fibroblasts. Furthermore, the inhibited Kupffer cells regenerated within 10 days after dosage withdrawal. Unlike carrier-free NIN treatment, CLD/NIN@LIEV induced a marked decrease in liver enzymes, indicating improved safety and anti-fibrosis efficacy. These results indicate its great potential for treatment with the combined anti-fibrosis agent and Kupffer cell inhibition strategies to enhance the liver fibrosis therapy.