Screening of siRNA Nanoparticles for Delivery to Airway Epithelial Cells Using high-content Analysis

Abstract

AIMS: Delivery of siRNA to the lungs via inhalation offers a unique opportunity to develop a new treatment paradigm for a range of respiratory conditions. However, progress has been greatly hindered by safety and delivery issues. This study developed a high-throughput method for screening novel nanotechnologies for pulmonary siRNA delivery. METHODOLOGY: Following physicochemical analysis, the ability of PEI-PEG-siRNA nanoparticles to facilitate siRNA delivery was determined using high-content analysis (HCA) in Calu-3 cells. Results obtained from HCA were validated using confocal microscopy. Finally, cytotoxicity of the PEI-PEG-siRNA particles was analyzed by HCA using the Cellomics multiparameter cytotoxicity assay. CONCLUSION: PEI-PEG-siRNA nanoparticles facilitated increased siRNA uptake and luciferase knockdown in Calu-3 cells compared with PEI-siRNA.