Multimerized siRNA Cross-linked by Gold Nanoparticles

In this study, siRNAs terminated with thiol groups were multimerized and cross-linked using ∼5 nm gold nanoparticles (AuNPs) via Au-S chemisorption that can be intracellularly reduced. AuNPs immobilized with single-stranded antisense siRNA were assembled with those with single-stranded sense siRNA via complementary hybridization or assembled with those with single-stranded dimeric sense siRNA. The multimerized siRNA cross-linked by AuNPs showed increased charge density and enhanced enzymatic stability, and exhibited good complexation behaviors with a polycationic carrier, linear polyethylenimine (L-PEI). The resultant multi-siRNA/AuNPs/L-PEI polyelectrolyte complexes exhibited far greater gene silencing efficiencies of green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF) compared to naked siRNA complexes. They could also be visualized by micro-CT imaging. The results suggest that AuNP-mediated multimerization of siRNAs could be a rational approach to achieve both gene silencing and imaging at a target tissue simultaneously.