Mechanisms of nucleotide trafficking during siRNA delivery to endothelial cells using perfluorocarbon nanoemulsions.
RNA interference (RNAi) is a useful in vitro research tool, but its application as a safe and effective therapeutic agent may benefit from improved understanding of mechanisms of exogenous siRNA delivery, including cell trafficking and sorting patterns. We report the development of a transfection reagent for siRNA delivery which employs a distinctive non-digestive mode of particle-cell membrane interaction through the formation of a hemifusion complex resulting in lipid raft transport of cargo to the cytosol, bypassing the usual endosomal nanoparticle uptake pathway. We further demonstrate markedly enhanced efficacy over conventional transfection agents for suppressing endothelial cell expression of upregulated vascular adhesion molecules.
Kaneda
Megan M
MM
Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63108, USA.
Sasaki
Yo
Y
Lanza
Gregory M
GM
Milbrandt
Jeffrey
J
Wickline
Samuel A
SA
D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D021961:Cell Membrane Structures / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004655:Emulsions / Q000737:chemistry*; D042783:Endothelial Cells / Q000378:metabolism*; D005466:Fluorocarbons / Q000737:chemistry*; D007202:Indicators and Reagents / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009711:Nucleotides / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods
D002412:Cations; D004337:Drug Carriers; D004655:Emulsions; D005466:Fluorocarbons; D007202:Indicators and Reagents; D008055:Lipids; C086724:Lipofectamine; D009711:Nucleotides; D034741:RNA, Small Interfering