Sharma Shivani, Rajendran Vinoth, Kulshreshtha Ritu, Ghosh Prahlad C
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi 110016, India.
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi 110021, India.
Int J Pharm. 2017 Sep 15;530(1-2):387-400. doi: 10.1016/j.ijpharm.2017.07.079. Epub 2017 Jul 31.
MicroRNAs are gaining rapid attention as promising targets for cancer treatment; however, efficient delivery of therapeutic miRNA or anti-miRNA into cancer cells remains a major challenge. Our previous work identified miR-191 as an oncogenic miRNA overexpressed in breast cancer that assists in progression of malignant transformation. Thus, inhibition of miR-191 using antisense miR-191 (anti-miR-191) has immense therapeutic potential. Here, we have developed a stearylamine (SA) based cationic liposome for delivery of miR-191 inhibitor (anti-miR-191), and studied its efficacy in breast cancer cells (MCF-7 and ZR-75-1) in culture. SA liposomes alone inhibited cancer cell growth with lesser IC (50% inhibitory concentration) values as compared to normal mouse fibroblast cells (L929). The efficient delivery of anti-miR-191 in SA liposome complex was found to be highly effective in killing the cancer cells than a comparable dose of SA free anti-miR-191 liposome complex. The formulation also showed negligible cytotoxicity in human erythrocytes. Combined treatment of SA liposome with anti-miR-191 markedly enhanced apoptotic cell death and suppressed the migration of cancer cells in vitro. Notably, anti-miR-191 loaded SA liposome complex increased chemosensitivity of breast cancer cells to currently used anti-cancer drugs (doxorubicin or cisplatin) in free form. Our work demonstrates that anti-miR-191 loaded in SA liposome complex has promising clinical application for breast cancer therapy.
微小RNA作为癌症治疗的潜在靶点正迅速受到关注；然而，将治疗性微小RNA或抗微小RNA有效递送至癌细胞仍然是一项重大挑战。我们之前的研究确定miR-191是一种在乳腺癌中过表达的致癌性微小RNA，它有助于恶性转化的进展。因此，使用反义miR-191（抗miR-191）抑制miR-191具有巨大的治疗潜力。在此，我们开发了一种基于硬脂胺（SA）的阳离子脂质体用于递送miR-191抑制剂（抗miR-191），并研究了其在培养的乳腺癌细胞（MCF-7和ZR-75-1）中的疗效。与正常小鼠成纤维细胞（L929）相比，单独的SA脂质体以较低的IC（50%抑制浓度）值抑制癌细胞生长。发现SA脂质体复合物中抗miR-191的有效递送在杀死癌细胞方面比同等剂量的不含SA的抗miR-191脂质体复合物更有效。该制剂在人红细胞中也显示出可忽略不计的细胞毒性。SA脂质体与抗miR-191联合治疗显著增强了凋亡细胞死亡并抑制了癌细胞在体外的迁移。值得注意的是，负载抗miR-191的SA脂质体复合物增加了乳腺癌细胞对目前使用的游离形式抗癌药物（阿霉素或顺铂）的化学敏感性。我们的工作表明，负载在SA脂质体复合物中的抗miR-191在乳腺癌治疗中具有广阔的临床应用前景。
