Exosomes and other extracellular vesicles-mediated microRNA delivery for cancer therapy

Abstract: Extracellular vesicles (EVs), including exosomes and microvesicles, are critical mediators of cellto- cell communication in tissue homeostasis and repair, both in physiological and pathological conditions. Recently, progress has been achieved in their use in regenerative medicine as transfer agents for active biomolecules. Specifically, EVs are natural carriers of microRNAs (miRNAs), protecting their cargo from plasma ribonucleases and delivering their content to recipient cells. Expression of miRNAs is dysregulated in virtually all forms of cancer. Therefore, EVs-mediated miRNA delivery may represent a valuable tool for cancer therapeutic intervention, aiming at restoring cancer miRNAs expression to normal levels. MicroRNAs may act both as tumor suppressors or oncogenes, consequently different alternative approaches for regulating miRNA expression in tumor tissues have been developed. Here, we review the various strategies for miRNA loading into EVs and highlight studies of EVs-mediated miRNA delivery which have been employed for cancer treatment, both in vitro and in vivo. Collectively, these data support the use of EVs in miRNAs/miRNAs antagonist transfer for cancer therapy, but challenges related to EV biology have yet to be further addressed before safe clinical translation.