Let-7 miRNA and CDK4 siRNA co-encapsulated in Herceptin-conjugated liposome for breast cancer stem cells

作     者：Jeong Hyun Shin Dae Hwan Shin Jin Seok Kim Jeong Hyun Shin;Dae Hwan Shin;Jin Seok Kim

作者机构：College of PharmacySookmyung Women’s UniversitySeoul 04310Republic of Korea College of PharmacyChungbuk National UniversityCheongju 28160Republic of Korea 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2020年第15卷第4期

页      面：472-481页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.2017R1D1A1B03030849) the National Research Foundation of Korea grant funded by the Korea Government(MEST,No.2011-0030074) 

主　　题：Let-7 miRNA CDK4 siRNA Liposomes Breast cancer stem cells 

摘      要：Recently,breast cancer stem cells(BCSCs)have rapidly emerged as a novel target for the therapy of breast cancer as they play critical roles in tumor growth,maintenance,metastasis,and ***-7 miRNA is known to be downregulated in a variety of cancers,especially BCSCs,whereas CDK4 being overexpressed in human epidermal growth factor receptor 2(HER-2)overexpressing tumor *** this study,let-7 miRNA and CDK4-specific siRNA were chosen as therapeutic agents and co-encapsulated in Herceptinconjugated cationic liposomes for breast cancer *** size,zeta potential,and encapsulation efficacy of mi/siRNA-loaded PEGylated liposome conjugated with Herceptin(Her-PEG-Lipo-mi/siRNA)were 176 nm,28.1 mV,and 99.7%±0.1%,*** cellular uptake(86%)was observed by fluorescence microscopy when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/***,the increased amount of let-7a mRNA and decreased amount of cellular CDK4 mRNA were observed by qRT-PCR when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/siRNA,which was even more so when SK-BR-3 stem cells were used(197 vs 768 times increase for let-7a,62%vs 68%decrease for CDK4).Growth inhibition(65%)andmigration arrest(0.5%)of the cellswere achieved by the treatment of the cells with Her-PEG-Lipo-mi/siRNA,but not withmi/siRNA complex or other *** conclusion,an efficient liposomal delivery system for the combination of miRNA and siRNA to target the BCSCs was developed and could be used as an efficacious therapeuticmodality for breast cancer.