Enhanced Cellular Delivery of siRNA via Micelle-Templated Dendritic Gold Nanoparticles

RNA interference (RNAi) has attracted considerable attention as a therapeutic strategy for difficult-to-treat and gene-associated diseases because of its ability to selectively silence target genes. However, the therapeutic application of small interfering RNA (siRNA) remains limited by enzymatic degradation, poor cellular uptake, and inefficient intracellular delivery. Therefore, successful siRNA delivery requires a carrier capable of forming stable complexes with siRNA, protecting it from enzymatic degradation, and promoting cellular uptake. In this study, micelle-templated dendritic gold nanoparticles (Au@MC) were investigated as siRNA delivery carriers. The branched architecture of Au@MC provides interbranch spaces capable of accommodating siRNA, thereby facilitating cellular uptake and enhancing gene-silencing activity. Among the tested formulations, the Au@MC-2/siRNA complex exhibited the most efficient gene silencing under both serum-free and serum-containing conditions while maintaining low cytotoxicity. The distinctive grooves of Au@MC may further protect siRNA against enzymatic degradation, thereby improving its serum stability and gene-silencing efficacy. These findings suggest that Au@MC represents a promising nanocarrier platform for safe and effective siRNA delivery.