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

Wong, Yunyi, Markham, Kathryn, Xu, Zhi Ping, Chen, Min, Liu, Gao Qing (Max), Bartlett, Perry F. and Cooper, Helen M. (2010) Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles. Biomaterials, 31 33: 8770-8779. doi:10.1016/j.biomaterials.2010.07.077

Author Wong, Yunyi
Markham, Kathryn
Xu, Zhi Ping
Chen, Min
Liu, Gao Qing (Max)
Bartlett, Perry F.
Cooper, Helen M.
Title Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles
Journal name Biomaterials   Check publisher's open access policy
ISSN 0142-9612
Publication date 2010-11-01
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.biomaterials.2010.07.077
Open Access Status Not Open Access
Volume 31
Issue 33
Start page 8770
End page 8779
Total pages 10
Place of publication The Netherlands
Publisher Elsevier BV
Language eng
Subject 1502 Bioengineering
2503 Ceramics and Composites
1304 Biophysics
2502 Biomaterials
2211 Mechanics of Materials
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. © 2010 Elsevier Ltd.
Keyword Central nervous system
Drug delivery
Layered double hydroxides
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Queensland Brain Institute Publications
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Created: Fri, 25 Feb 2011, 02:39:42 EST by Debra McMurtrie on behalf of Queensland Brain Institute