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Nanotechnology approach for drug addiction therapy: gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons

Authors :
Bonoiu, Adela C.
Mahajan, Supriya D.
Ding, Hong
Roy, Indrajit
Yong, Ken-Tye
Kumar, Rajiv
Hu, Rui
Bergey, Earl J.
Schwartz, Stanley A.
Prasad, Paras N.
Source :
Proceedings of the National Academy of Sciences of the United States. April 7, 2009, Vol. 106 Issue 14, p5546, 5 p.
Publication Year :
2009

Abstract

Drug abuse is a worldwide health concern in which addiction involves activation of the dopaminergic signaling pathway in the brain. Here, we introduce a nanotechnology approach that utilizes gold nanorod-DARPP-32 siRNA complexes (nanoplexes) that target this dopaminergic signaling pathway in the brain. The shift in the localized longitudinal plasmon resonance peak of gold nanorods (GNRs) was used to show their interaction with siRNA. Plasmonic enhanced dark field imaging was used to visualize the uptake of these nanoplexes in dopaminergic neurons in vitro. Gene silencing of the nanoplexes in these cells was evidenced by the reduction in the expression of key proteins (DARPP-32, ERK, and PP-1) belonging to this pathway, with no observed cytotoxicity. Moreover, these nanoplexes were shown to transmigrate across an in vitro model of the blood-brain barrier (BBB). Therefore, these nanoplexes appear to be suited for brain-specific delivery of appropriate siRNA for therapy of drug addiction and other brain diseases. DARPP-32 | dark field imaging | surface plasmon resonance | nanoplexes | blood-brain barrier

Details

Language :
English
ISSN :
00278424
Volume :
106
Issue :
14
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.198472589