Nanoparticle Delivery of miRNA in Cancer

MicroRNAs (miRNAs) have emerged as crucial mediators of a wide range of physiological and biological processes, their dysregulation was shown to contribute to the pathogenesis of human diseases, including cancer. To date, more than 2200 differentially expressed miRNAs have been identified in 36 different human cancer types. miRNAs are a class of small non-coding RNAs that regulate post-transcriptional gene expression by sequence-specific binding to the 3′ untranslated region and suppressing target mRNA expression. Recently, interest in miRNA-based therapeutics has increased significantly as miRNAs provide a remarkable therapeutic tool for silencing genes/oncogenes that play roles in proliferation, metastasis, drug resistance, apoptosis, angiogenesis, metabolism, leading to tumor growth and progression. For oncogenic miRNAs, which are often overexpressed in cancers and inhibit tumor suppressor genes, therapeutic applications involve inhibition of them using antagomiRs. Given the unprecedented hope for personalized cancer treatment, this new class of specific therapeutics offer highly targeted therapeutic interventions. However, successful clinical applications of miRNA-based therapeutics are challenging and require the development of nanodelivery systems to overcome degradation of miRNAs by nucleases, their low cellular uptake, immunogenicity, and rapid renal clearance. Here, we review potential approaches for systemic delivery of miRNAs for cancer therapy and focus on nanocarriers used for the delivery of miRNAs into tumors.