siRNA Delivery Using Nanocarriers – An Efficient Tool for Gene Silencing

Abstract

Small interfering RNAs (siRNA) are one of the most recent additions used to silence gene expression. At present siRNA is the most extensively used gene-silencing technique over other nucleic-acid based approaches to treat disease including cancer, hepatitis, respiratory disease, cardiovascular diseases, neuronal disease and autoimmune disease. However, systemic delivery of siRNA in vivo, remains to be the biggest challenge to be overcome. Various strategies have been developed to deliver siRNA efficiently into target cell such as chemical modification of siRNA, physical strategies, viral and non viral-vectors mediated delivery. Among all the approaches non viral vectors including lipoplexes and polyplexes were found to be most successful which have been reviewed in this article. Further therapeutic applications of RNAi have also been briefly reviewed.

Nanoparticle-delivered VEGF-silencing cassette and suicide gene expression cassettes inhibit colon carcinoma growth in vitro and in vivo

“…Importantly, systemic delivery of CPNP-shVEGF-CDTK established high efficacy in delaying tumor growth in xenograft colon carcinoma animal model. This might benefit from the properties of CPNP, such as positive surface charges, protection of the encapsulated plasmid DNA, and low toxicity [8][9][10][11]. The nanoparticles with positive surface charges are preferentially taken by the tumor cells and are retained longer than negatively charged or neutral particles [8,9].…”

“…We have developed calcium phosphate nanoparticles (CPNPs) with modified surface made of calcium chloride, which can either efficiently delivery DNA or protect DNA from degradation [10]. Moreover, CPNP has excellent biocompatibility and can be reabsorbed by the body with limited toxicity and few obvious side effects [10,11].…”

Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors

“…These were mainly directed to specific aspects of the compaction process, as the molecular characteristics of the hydrophobic regions and/or headgroups, and of the lipoplex structure [11,15,[20][21][22][23][24][25], the biochemical behavior [26][27][28][29][30], the structure-biological activity relationship [9,21,[31][32][33][34][35], or to several of them [7,8,10,13,36,37]. On the other hand, several reviews have been centered in polyplexes [14,[38][39][40][41] or in a wide variety of nanocarriers [16,17,[42][43][44]. The present review summarizes the biophysics and biochemistry studies carried on in the present decade with multivalent cationic gene vectors.…”

“…Its objective is to transfect nucleic acids (DNA or RNA) for curing human disease at a molecular level following one of these two possibilities: (i) repairing damaged cellular DNA by inserting and expressing appropriate DNA into the cells for performing the pre-designed activity [6][7][8][9][10][11][12][13][14][15]; or (ii) silencing the defective gene by inserting short interfering RNA (siRNA) to knockdown and stop the expression of the pathogenic protein [14,16,17]. The negative charge of plasmid DNA and RNA polyelectrolytes limits its transport through the cell membrane (also negatively charged) being necessary the use of gene vectors for compacting and transporting them into the cells.…”

siRNA transfection by dendritic core–shell nanocarriers

“…Moreover, it lacks the ability to penetrate the cellular lipid membranes due to its negative charge, resulting in poor cellular uptake and 1 Introduction pharmacokinetics. [63][64][65] Therefore, successful application of RNA interference in mammalian cells requires an efficient transfection agent that will enhance their pharmacological properties. [39] The appropriate delivery system should be able to: (i) complex/condense the siRNA, (ii) facilitate targeting to and uptake into the target cells, (iii) protect it from degradation through serum nucleases, and (iv) promote trafficking to the cytoplasm to provide the siRNA in clinically relevant doses.…”