Mechanisms of nucleotide trafficking during siRNA delivery to endothelial cells using perfluorocarbon nanoemulsions

Megan M. Kaneda, Yo Sasaki, Gregory M. Lanza, Jeffrey Milbrandt, Samuel A. Wickline

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish
Pages (from-to)3079-3086
Number of pages8
JournalBiomaterials
Volume31
Issue number11
DOIs
StatePublished - Apr 1 2010

Keywords

  • Drug delivery
  • Endothelial cell
  • Gene therapy
  • Nanoparticle

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