Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.
Pharmaceutical Nanotechnology Department, Shiraz University of Medical Sciences, Shiraz 71345, Iran.
Curr Pharm Des. 2018;24(31):3678-3696. doi: 10.2174/1381612825666181120160316.
MicroRNAs are small noncoding RNAs with key roles in gene expression. It has been revealed that aberrant expression of microRNAs is related to gene expression abnormality, and they have the potential to be used as anti-cancer drugs. However, the delivery of microRNAs is limited due to barriers, such as low uptake and insufficient endosomal release, intracellular nucleases degradation, phagocytic elimination, and renal filtration. To overcome these issues, novel delivery systems are developed for improving the efficiency of microRNAs therapy ranging from viral to synthetic; some are further developed with targeted ligands for active targeting purposes. Such delivery systems provide efficient cellular uptake and endosomal release as well as low cytotoxicity and minimum unwanted host immune response. Nevertheless, more complementary studies are warranted before being applied in human studies. This review deals with recent updates on the challenges and achievements of the various nanotechnology-based gene delivery vehicles with a special emphasis on the miRNA delivery in cancer therapy. In addition, we attempted to categorize the designed delivery systems based on miRNA therapeutic molecule. The related cellular signaling pathways and pharmacological action against cancer promotion have also been highlighted.
微小 RNA 是一种小的非编码 RNA，在基因表达中具有关键作用。已经揭示，微小 RNA 的异常表达与基因表达异常有关，它们有可能被用作抗癌药物。然而，由于摄取率低、内体释放不足、细胞内核酶降解、吞噬消除和肾过滤等障碍，微小 RNA 的传递受到限制。为了克服这些问题，开发了新型的传递系统，以提高微小 RNA 治疗的效率，范围从病毒到合成；一些系统进一步开发了靶向配体，以达到主动靶向的目的。这些传递系统提供了高效的细胞摄取和内体释放，以及低细胞毒性和最小的不必要的宿主免疫反应。然而，在应用于人体研究之前，还需要进行更多的补充研究。本综述涉及基于纳米技术的各种基因传递载体的挑战和成就的最新进展，特别强调微小 RNA 在癌症治疗中的传递。此外，我们试图根据微小 RNA 治疗分子对设计的传递系统进行分类。还强调了相关的细胞信号通路和对抗癌促进的药理学作用。
