title: Mechanisms of nucleotide trafficking during siRNA delivery to endothelial cells using perfluorocarbon nanoemulsions.
abstract: 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.
authors.affiliation: Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Kaneda
authors.forename: Yo
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
mesh_terms: 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
chemical_list: D002412:Cations; D004337:Drug Carriers; D004655:Emulsions; D005466:Fluorocarbons; D007202:Indicators and Reagents; D008055:Lipids; C086724:Lipofectamine; D009711:Nucleotides; D034741:RNA, Small Interfering