Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing
| Autor: | Amanda P. Malefyt, Kwasi Adu-Berchie, Christina Chan, Daniel Vocelle, Olivia M. Chesniak, S. Patrick Walton, Georgina Comiskey, Milton R. Smith |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Small interfering RNA biology 02 engineering and technology 021001 nanoscience & nanotechnology Endocytosis Molecular biology Clathrin Article Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Dextran chemistry RNA interference biology.protein Gene silencing Scavenger receptor 0210 nano-technology Intracellular |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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