| Autor: |
Vasher MK; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States., Evangelopoulos M; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States., Mirkin CA; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.; Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States. |
| Abstrakt: |
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 in vitro 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. |
