Three decades have passed from the initial discovery of a microRNA (miRNA) in Caenorhabditis elegans to our current understanding that miRNAs play essential roles in regulating fundamental physiological processes and that their dysregulation can lead to many human pathologies, including cancer. In effect, restoration of miRNA expression or downregulation of aberrantly expressed miRNAs using miRNA mimics or anti-miRNA inhibitors (anti-miRs/antimiRs), respectively, continues to show therapeutic potential for the treatment of cancer. Although the manipulation of miRNA expression presents a promising therapeutic strategy for cancer treatment, it is predominantly reliant on nucleic acid-based molecules for their application, which introduces an array of hurdles, with respect to in vivo delivery. Because naked nucleic acids are quickly degraded and/or removed from the body, they require delivery vectors that can help overcome the many barriers presented upon their administration into the bloodstream. As such, in this review, we discuss the strengths and weaknesses of the current state-of-the-art delivery systems, encompassing viral- and nonviral-based systems, with a specific focus on nonviral nanotechnology-based miRNA delivery platforms, including lipid-, polymer-, inorganic-, and extracellular vesicle-based delivery strategies. Moreover, we also shed light on peptide carriers as an emerging technology that shows great promise in being a highly efficacious delivery platform for miRNA-based cancer therapeutics.
Keywords: CPPs; RNA silencing; cancer; cell-penetrating peptides; miRNA delivery; miRNA therapeutics; microRNA.