Spherical Gold Nanoparticles: Small Interfering RNA Delivery in Regulation of the Tumor Necrosis Factor-Alpha Gene Expression

Abstract

Proinflammatory cytokines are signaling molecules that are expelled from immune cells like macrophages and other types of cells. Tumor necrosis factor-alpha (TNF-α) is overexpressed during inflammation caused by inflammatory diseases. Therefore, the regulation of TNF-α has a key role in inflammation. The use and target delivery of small interfering RNAs (siRNAs) provide many effectual treatment benefits in the regulation of gene expression in cells. In this study, we used siRNA nanoparticle conjugates in the regulation of gene expression and inflammation. We first prepared safe fusion ribonucleic acid interference carrier, spherical nucleic acid nanoparticle conjugates (SNA-NCs), to enhance the perforation of siRNA into the macrophages and their ability to target TNF-α gene regulation. Furthermore, the suppression of the TNF-α gene was monitored after curing macrophages by SNA-NCs. Gene expression was carried out by real-time polymerase chain reaction in cells and the levels of TNF-α were investigated by the enzyme-linked immunosorbent assay (ELISA) method. This study indicated that the SNA-NCs were safe and very stable. TNF-α siRNA could significantly regulate gene expression in cells to form SNA-NCs. The results indicated that TNF-α gene expression downregulated to 93.40% ± 1.45%, 66.06% ± 0.95%, and 35.76% ± 1.09% in the presence of 0.1, 1, and 10 nM siRNA, respectively. The proliferation of macrophages and subsequently expression of TNF-α were significant for the formation of inflammation. These findings showed that the use of SNA-NC siRNA might ameliorate the inflammatory disease by suppression of gene expression and functional activity of macrophage generation.