Synthetic poly(ester amine) and poly(amido amine) nanoparticles for efficient DNA and siRNA delivery to human endothelial cells

Abstract

Stephany Y Tzeng, Peter H Yang, Warren L Grayson, Jordan J GreenDepartment of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: Biodegradable poly(ester amine) (PEA)-based and poly(amido amine) (PAA)-based nanoparticles were developed for efficient in vitro siRNA delivery to human umbilical vein endothelial cells (HUVECs). They were screened, characterized, and compared with traditionally studied DNA-containing particles. Several of the polymeric nanoparticles tested were found to be effective for delivering functional siRNA to green fluorescent protein (GFP) + HUVECs, achieving 60%–75% GFP knockdown while maintaining high viability. While PEAs have been used previously to form polyplexes or nanoparticles for DNA delivery, highly effective siRNA delivery in hard-to-transfect human cell types has not been previously reported. PEAs and linear nondendrimeric PAAs were also found to be effective for DNA delivery to HUVECs using GFP-encoding plasmid DNA (up to 50%–60% transfection efficiency). PEAs and PAAs can be separated into groups that form polymeric nanoparticles effective for siRNA delivery, for DNA delivery, or for both.Keywords: nanoparticles, siRNA, DNA, gene delivery, human umbilical vein endothelial cells