title: Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing.
abstract: Understanding the endocytosis and intracellular trafficking of short interfering RNA (siRNA) delivery vehicle complexes remains a critical bottleneck in designing siRNA delivery vehicles for highly active RNA interference (RNAi)-based therapeutics. In this study, we show that dextran functionalization of silica nanoparticles enhanced uptake and intracellular delivery of siRNAs in cultured cells. Using pharmacological inhibitors for endocytotic pathways, we determined that our complexes are endocytosed via a previously unreported mechanism for siRNA delivery in which dextran initiates scavenger receptor-mediated endocytosis through a clathrin/caveolin-independent process. Our findings suggest that siRNA delivery efficiency could be enhanced by incorporating dextran into existing delivery platforms to activate scavenger receptor activity across a variety of target cell types.
authors: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Daniel
authors: D
authors: Vocelle
authors: Department of Chemistry, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Olivia M
authors: OM
authors: Chesniak
authors: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Amanda P
authors: AP
authors: Malefyt
authors: Department of Chemistry, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Georgina
authors: G
authors: Comiskey
authors: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Kwasi
authors: K
authors: Adu-Berchie
authors: Department of Chemistry, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Milton R
authors: MR
authors: Smith
authors: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: Christina
authors: C
authors: Chan
authors: Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824-1226, USA.
authors: S Patrick
authors: SP
authors: Walton
keywords: Caveolin; Clathrin; Confocal Microscopy; Delivery Vehicles; Dextran; Endocytosis; H1299; HeLa; Lung Carcinoma; Nanoparticles; RNA Interference; RNAi; Scavenger Receptors; Silica; siRNAs