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Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
8862 608 2010 10 PDF Available
Title
Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles
Abstract

Small interfering RNAs (siRNAs) are capable of targeting and destroying specific mRNAs, making them particularly suited to the treatment of neurodegenerative conditions such as Huntington’s Disease where the production of abnormal proteins results in a gain-of-function phenotype. Although a variety of nanoparticle formulations are currently under development as siRNA delivery systems, application of these technologies has been limited by their high cytotoxicity, low drug loading capacity and release, and inability to penetrate cell membranes. Layered double hydroxide (LDH) nanoparticles are now emerging as a potential new drug delivery system as they exhibit low cytotoxicity and are highly biocompatible. Here we present the first study investigating LDH delivery of siRNAs to primary cultured neurons. We show that internalization by neurons is rapid, dose-dependent and saturable, and markedly more efficient than in other cell types. We demonstrate that siRNA–LDH complexes are internalized by clathrin-dependent endocytosis at the cell body and in neurites, with subsequent retrograde transport to the cell body followed by efficient release into the cytoplasm. Finally we show that LDH mediated siRNA delivery effectively silences neuronal gene expression. This study therefore confirms the potential of LDH nanoparticles as a drug delivery system for patients suffering from neurodegenerative disease.

Keywords
Layered double hydroxides; Nanoparticle; Drug delivery; siRNA; Neuron; Central nervous system
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Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 33, November 2010, Pages 8770–8779
Authors
, , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us