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Overcoming obstacles in microRNA delivery towards improved cancer therapy

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Abstract

MicroRNAs (miRNAs) are small noncoding RNAs found to govern nearly every biological process. They frequently acquire a gain or a loss of function in cancer, hence playing a causative role in the development and progression of cancer. There are major obstacles on the way for the successful delivery of miRNA, which include low cellular uptake of the RNA and endosomal escape, immunogenicity, degradation in the bloodstream, and rapid renal clearance. The delivered miRNA needs to be successfully routed to the target organ, enter the cell and reach its intracellular target in an active form. Consequently, in order to exploit the promise of RNA interference, there is an urgent need for efficient methods to deliver miRNAs. These can be divided into three main categories: complexation, encapsulation, and conjugation. In this review, we will discuss the special considerations for miRNA delivery for cancer therapy, focusing on nonviral delivery systems: lipid, polymeric, and inorganic nanocarriers.

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Acknowledgments

We would like to thank Dr Noga Yerushalmi for critical appraisal of the manuscript. The Satchi-Fainaro research laboratory is partially supported by The Association for International Cancer Research (AICR), German-Israel Foundation (GIF), The Marguerite Stolz Research Fund for outstanding faculty, Rimonim Consortium and the MAGNET Program of the Office of the Chief Scientist of the Israel Ministry of Industry, Trade & Labor, THE ISRAEL SCIENCE FOUNDATION (grant no. 1309/10), the US–Israel Binational Science Foundation (grant no. 2007347), Swiss Bridge Award, and by grants from the Israeli National Nanotechnology Initiative (INNI), Focal Technology Area (FTA) program: Nanomedicine for Personalized Theranostics, and by The Leona M. and Harry B. Helmsley Nanotechnology Research Fund.

Conflict of interest statement

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Dikla Ben-Shushan, Ela Markovsky, Hadas Gibori, Galia Tiram, Anna Scomparin & Ronit Satchi-Fainaro

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  1. Dikla Ben-Shushan
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  2. Ela Markovsky
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  3. Hadas Gibori
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  4. Galia Tiram
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Correspondence to Ronit Satchi-Fainaro.

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D. Ben-Shushan, E. Markovsky, and H. Gibori contributed equally to this manuscript.

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Ben-Shushan, D., Markovsky, E., Gibori, H. et al. Overcoming obstacles in microRNA delivery towards improved cancer therapy. Drug Deliv. and Transl. Res. 4, 38–49 (2014). https://doi.org/10.1007/s13346-013-0160-0

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