Broadening the Horizons of RNA Delivery Strategies in Cancer Therapy

Abstract

RNA-based therapy is a promising and innovative strategy for cancer treatment. However, poor stability, immunogenicity, low cellular uptake rate, and difficulty in endosomal escape are considered the major obstacles in the cancer therapy process, severely limiting the development of clinical translation and application. For efficient and safe transport of RNA into cancer cells, it usually needs to be packaged in appropriate carriers so that it can be taken up by the target cells and then be released to the specific location to perform its function. In this review, we will focus on up-to-date insights of the RNA-based delivery carrier and comprehensively describe its application in cancer therapy. We briefly discuss delivery obstacles in RNA-mediated cancer therapy and summarize the advantages and disadvantages of different carriers (cationic polymers, inorganic nanoparticles, lipids, etc.). In addition, we further summarize and discuss the current RNA therapeutic strategies approved for clinical use. A comprehensive overview of various carriers and emerging delivery strategies for RNA delivery, as well as the current status of clinical applications and practice of RNA medicines are classified and integrated to inspire fresh ideas and breakthroughs.

RNA Vaccines: Yeast as a Novel Antigen Vehicle

“…However, the success of this strategy involves both the effectiveness of silencing and the nonoccurrence of toxic effects. Thus, some adaptations are performed, including chemical modifications and changes in size, charge, and hydrophilicity that can interfere with the cellular uptake and biodistribution of RNAi molecules [77]. The administration method and the particle size of the vehicle influence the bioavailability and biodistribution of the loaded RNAi.…”

“…In this sense, the efficiency of this approach also depends on the use of efficient delivery systems [66,77]. Liposomes, bacteria, and viruses are examples of platforms used as vehicles for interfering RNAs, as well as already used for DNA and mRNA vaccines [78 -80].…”

“…The therapeutic interfering RNA can be eliminated from the body in hours or days, even if it is nanoparticulate. The reduced bioavailability time may be insufficient for the immunotherapeutic product not to reach the target cells or tissues [77]. On the other hand, Zhang et al (2014) analyzed the immune response of mice with CD40 shRNA carried by S. cerevisiae 50 days after oral administration, observing the continuity of the effects of the CD40 receptor silencing about the set of cytokines present in the blood and from the extraction of proteins and dendritic cells from the intestine of immunized animals [66].…”

miRNA‐21 Inhibitor‐Loaded Cationic Liposomes Development using the Quality by Design Approach

“…Therefore, knockdown of miR‐21 could lead to an increase in apoptotic cell death [12–14] . Naked miRNA transfer in cells is problematic due to a series of reasons, including rapid degradation by RNases and extremely poor membrane permeability, to which the risk of off‐target effects can be added [15–17] . Successful gene therapy requires an efficient delivery of genetic material in the target cells [10] .…”

“…[12][13][14] Naked miRNA transfer in cells is problematic due to a series of reasons, including rapid degradation by RNases and extremely poor membrane permeability, to which the risk of off-target effects can be added. [15][16][17] Successful gene therapy requires an efficient delivery of genetic material in the target cells. [10] Therefore, the crucial step in gene therapy is choosing the appropriate vector for specific RNA delivery into the target cell.…”