Transforming Hairpin-like SiRNA-Based Spherical Nucleic Acids into Biocompatible Constructs

The design and synthesis of hairpin-like small interfering RNA spherical nucleic acids (siRNA-SNAs) based upon biocompatible liposome nanoparticle cores are described. The constructs were characterized by gel electrophoresis, dynamic light scattering, and OliGreen-based oligonucleotide quantification. These siRNA-SNA nanoconstructs enter cells 20-times more efficiently than linear siRNA in as little as 4 h, while exhibiting a 4-fold reduction in cytotoxicity compared with conventional siRNA-SNAs composed of gold nanoparticle cores. Importantly, these siRNA-SNA constructs effectively inhibit angiogenesis by silencing vascular endothelial growth factor, a key mediator of angiogenesis in a multitude of diseases, in human umbilical vein endothelial cells. This work shows how hairpin architectures can be chemically incorporated into biocompatible SNAs in a way that retains advantageous SNA properties and maximizes gene regulation capabilities.