Improving the therapeutic efficiency of noncoding RNAs in cancers using targeted drug delivery systems

•The role of non-coding RNA in treating various cancers is emphasized.•Recent advances in drug delivery systems to enhance ncRNA stability and efficiency are reviewed.•Clinical applications of miRNA and its potential use is discussed. The delivery of noncoding (nc)RNA to target cancer stem cells and metastatic tumors has shown many positive outcomes, resulting in improved and more efficient treatment strategies. The success of therapeutic RNA depends solely on passing cellular barriers to reach the target site, where it binds to the mRNA of the interest. By 2018, 20 clinical trials had been initiated, most focusing on cancer and diabetes, with some progressing to Phase II clinical trials testing the safety and efficacy of small interfering (si)RNA. Many challenges limit RNA interference (RNAi) and miRNA usage in vivo; therefore, various approaches have been developed to promote ncRNA efficiency and stability. In this review, we focus on targeting the tumor microenvironment (TME) via the modification of delivery systems utilizing nanotechnology-based delivery approaches. Drug delivery systems can be utilized to enhance the stability and efficiency of noncoding (nc)RNA, which has a potential role in cancer therapy. Here, we discuss the ability of ncRNA to target tumor microenvironments via modification of a variety of delivery systems utilizing nanotechnology-based delivery approaches.