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

• 作者: Dae Hwan Shin Jeong Hyun Shin Jin Seok Kim
• 来源期刊: 亚洲药物制剂科学(英文)
• 学科: 医学
• 关键词: Let-7 miRNA CDK4 siRNA Liposomes Breast cancer stem cells
• 年，卷（期）: 2020,（4）
• 页码范围: 472-481
• 页数: 10页
• 分类号: R73

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 recurrence.Let-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 cells.In this study,let-7 miRNA and CDK4-specific siRNA were chosen as therapeutic agents and co-encapsulated in Herceptinconjugated cationic liposomes for breast cancer therapy.Particle 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%,respectively.Enhanced cellular uptake(86%)was observed by fluorescence microscopy when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/siRNA.Also,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 formulations.In 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.