Once considered genetic “oddities”, microRNAs (miRNAs) are now recognized as key epigenetic regulators of
numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer.
The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of
the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept,
but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical
(e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization
and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to
the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be
placed on how the current leading antimiR platforms—ranging from naked chemically modified oligonucleotides to
nanoscale delivery vehicles—are affected by and overcome these barriers. The perplexity of antimiR delivery presents
both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological
benefits of antagonizing tumor-associated miRNAs.
Keywords: AntimiR, cancer therapy, chemical modification, microRNA inhibition, liposome, polymer nanoparticle, oligonucleotide,
oncomiR, antisense therapeutics, tumor targeting.
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