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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.

SUBMITTER: Vocelle D

PROVIDER: S-EPMC5072529 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing.

Vocelle Daniel D Chesniak Olivia M OM Malefyt Amanda P AP Comiskey Georgina G Adu-Berchie Kwasi K Smith Milton R MR Chan Christina C Walton S Patrick SP

Technology 20160331 1

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 endoc ...[more]

PMID: 27774502

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