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Review
. 2018 Feb;10(1):69-86.
doi: 10.1007/s12551-017-0392-1. Epub 2018 Jan 11.

Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer

Tamkin Ahmadzada  1 , Glen Reid  2   3 , David R McKenzie  4
Affiliations
Review

Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer

Tamkin Ahmadzada et al. Biophys Rev. 2018 Feb.

Abstract

Gene silencing via RNA interference (RNAi) is rapidly evolving as a personalized approach to cancer treatment. The effector molecules-small interfering RNAs (siRNAs) and microRNAs (miRNAs)-can be used to silence or "switch off" specific cancer genes. Currently, the main barrier to implementing siRNA- and miRNA-based therapies in clinical practice is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver to them to tumor tissue, and release them into the cytoplasm of the target cancer cells, all without inducing adverse effects. Here, we review the fundamentals of RNAi, cell membrane transport pathways, and factors that affect intracellular delivery. We discuss the advantages and disadvantages of the various types of nanoparticle delivery systems, with a focus on those that have been investigated in breast cancer in vivo.

Keywords: Breast cancer; Cellular transport; Delivery; MicroRNA; Nanoparticles; siRNA.

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Conflict of interest statement

Conflict of interest

Tamkin Ahmadzada declares that she has no conflict of interest. Glen Reid declares that he has no conflict of interest. David McKenzie declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
Gene silencing using siRNA or miRNA mimics. Once the siRNA or miRNA mimic has been introduced into the cytoplasm of the cell, it is unwound and the active antisense strand (green) is incorporated into the RISC. This leads to gene silencing via two distinct mechanisms, depending on the extent of base pairing between the antisense strand and the target mRNA. With siRNA on the left, the complete homology between the antisense and target mRNA (yellow) leads to site-specific cleavage and degradation of the mRNA. In contrast, the partial sequence identity between the active miRNA strand and its mRNA target leads to inhibition of translation, decapping, and subsequent mRNA degradation
Fig. 2
Fig. 2
Schematic representation of delivery vehicles. Liposomes and micelles encapsulate siRNA/miRNA within an aqueous compartment, whereas dendrimers condense RNA via cationic interactions with positive charges on the surface. For simplicity, the major differences between liposomes, micelles, and dendrimers are depicted; as discussed in the text, variations exist in the composition of all three, for example through PEGylation and addition of targeting moieties
See this image and copyright information in PMC

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