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.
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.
Authors: Jerome Gilleron; Prasath Paramasivam; Anja Zeigerer; William Querbes; Giovanni Marsico; Cordula Andree; Sarah Seifert; Pablo Amaya; Martin Stöter; Victor Koteliansky; Herbert Waldmann; Kevin Fitzgerald; Yannis Kalaidzidis; Akin Akinc; Martin A Maier; Muthiah Manoharan; Marc Bickle; Marino Zerial Journal: Nucleic Acids Res Date: 2015-07-28 Impact factor: 16.971