文献类型：期刊文献

英文题名：EpCAM Aptamer-Functionalized Cationic Liposome-Based Nanoparticles Loaded with miR-139-5p for Targeted Therapy in Colorectal Cancer

作者：Zhao, Yuyu[1,2];Xu, Jiajun[3];Van Minh Le[4];Gong, Qianyi[1,2];Li, Shaoyu[5];Gao, Feng[3,6,7];Ni, Lei[8];Liu, Jianwen[1,2];Liang, Xin[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[4]Natl Inst Med Mat, Res Ctr Ginseng & Med Mat, Ho Chi Minh City, Vietnam;[5]Xinjiang Med Univ, Affiliated Hosp 3, Dept Clin Lab, Urumqi, Xinjiang, Peoples R China;[6]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[7]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[8]Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Respirat, 197 Ruijin Rd 2, Shanghai 200025, Peoples R China

年份：2019

卷号：16

期号：11

起止页码：4696

外文期刊名：MOLECULAR PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000494894300025)】；

基金：This work was financially supported by the Science and Technology Commission of Shanghai Municipality (no. 17430741600) and the National Natural Science Foundation of China (no. 81860378, 81873050).

语种：英文

外文关键词：nanoparticle; CRC; targeted therapy; miR-139-5p

摘要：Colorectal cancer (CRC) is one of the most common cancers worldwide. MicroRNAs (miRNAs) play a vital role in a variety of biology processes. Our previous work identified miR-139-5p as a tumor suppressor gene overexpressed in CRC that assisted in inhibiting progression of cancer. The main challenge of miRNAs as therapeutic agents is their rapid degradation in plasma, poor uptake, and off-target effects. Therefore, the development of miRNA-based therapies is necessary. In this study, we developed a cationic liposome-based nanoparticle loaded with miR-139-5p (miR-139-5p-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MNPs) and surface-decorated with epithelial cell adhesion molecule (EpCAM) aptamer (Apt) (miR-139-5p-EpCAM Apt-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MANPs) for the targeted treatment of CRC. The size of MANPs was 150.3 +/- 8.8 nm, which had a round-shaped appearance and functional dispersion capabilities. It also showed negligible hemolysis in the blood. MANPs markedly inhibited the proliferation, migration, and invasion of one or more CRC cell lines in vitro. Furthermore, we demonstrated the uptake and targeting ability of MANPs in vivo and in vitro. MANPs inhibit the growth of HCT8 cells in vitro and have a significant tumor suppressive effect on subcutaneous HCT8 colorectal tumor mice. Our results demonstrated that MANPs were an effective carrier approach to deliver therapeutic miRNAs to CRC.