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

The design and synthesis of hairpin-likesmall interfering RNAspherical nucleic acids (siRNA-SNAs) based upon biocompatible liposomenanoparticle cores are described. The constructs were characterizedby gel electrophoresis, dynamic light scattering, and OliGreen-basedoligonucleotide quantification. These siRNA-SNA nanoconstructs entercells 20-times more efficiently than linear siRNA in as little as4 h, while exhibiting a 4-fold reduction in cytotoxicity comparedwith conventional siRNA-SNAs composed of gold nanoparticle cores.Importantly, these siRNA-SNA constructs effectively inhibit angiogenesis in vitro by silencing vascular endothelial growth factor,a key mediator of angiogenesis in a multitude of diseases, in humanumbilical vein endothelial cells. This work shows how hairpin architecturescan be chemically incorporated into biocompatible SNAs in a way thatretains advantageous SNA properties and maximizes gene regulationcapabilities.