Advances in RNA cancer therapeutics: New insight into exosomes as miRNA delivery

Abstract

Advances in RNA cancer therapeutics: New insight into exosomes as miRNA delivery Luca Volpini a, Federica Monaco b, Lory Santarelli a, Jiri Neuzil c,d,e,*, Marco Tomasetti a,** a Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/a, 60020, Ancona, Italy b Department of Excellence SBSP-Biomedical Sciences and Public Health, Polytechnic University of Marche, Via Tronto 10/a, 60020, Ancona, Italy c School of Pharmacy and Medical Science, Griffith University, Southport, Australia d Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic e Faculty of Science and 1st Medical Faculty, Charles University, Prague, Czech Republic A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: MiRNA MiRNA-based therapeutics MiRNA delivery system RNA-based therapies Cancer treatment Exosomes A B S T R A C T We are now entering a new era of RNA therapies, such that mRNA-based vaccines and RNA interference approaches such as siRNA have already been launched on the pharmaceutical market. However, there are no FDAapproved RNA-based therapeutics for cancer treatment. Among RNA molecules, miRNAs represent a promising solution against cancer. Despite the ability to target multiple pathways, miRNA-based therapeutics struggle to reach phase 3 clinical trial. A reason of this delay is linked to complications of selective administration of miRNAs to their target, the tumor cell. Because of this, an efficient delivery system is necessary. In this sense, exosomes are considered the most promising miRNA-based therapeutic carriers in terms of safety and efficient cargo delivery. Furthermore, researchers have developed a new strategy to overcome the tumor capacity by using exosomes to release unnecessary miRNAs, shedding light on a new generation therapy of cancer treatment. The review describes recent advances in the application of miRNAs in the treatment of cancer, the use of exosomes for miRNA delivery, focusing on new approaches to overcome the limits of miRNA-loaded exosomes in clinical applications.