Micelle-templated dendritic gold nanoparticles for enhanced cellular delivery of siRNA

Successful cellular delivery of synthetic siRNA depends mainly on the capability of a carrier to form a stable complex with siRNA, which can provide efficient protection of the siRNA from enzyme-mediated degradation and improved cellular uptake. However, due to its short length and rigid structure, cellular delivery of siRNA is often not as efficient as that of plasmid DNA using conventional cationic polymer- and lipid-based carriers. Herein, we synthesized a dendritic gold nanoparticle (Au@MC)-based siRNA delivery system, which provides efficient protection of siRNA and improved cellular uptake. The Au@MC can be readily synthesized from a block copolymer micelle template with a dendritic structure. Au@MC can efficiently form a stable complex with the short and rigid siRNA by localizing it in the space between the branches of the Au@MC. The stability and cellular uptake efficiency were significantly influenced by the structural features of Au@MC, such as size, surface charge, and gap width between the branches. A selected Au@MC/siRNA formulation could successfully achieve highly efficient siRNA transfection in the absence and presence of serum proteins without significant cell toxicity, suggesting the formulation as a potential candidate for siRNA-based clinical gene therapy.