Nanotechnology approach for drug addiction therapy: gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons.
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.
Bonoiu
Adela C
AC
Institute for Lasers Photonics and Biophotonics, The State University of New York, Buffalo, NY 14260, USA.
Mahajan
Supriya D
SD
Ding
Hong
H
Roy
Indrajit
I
Yong
Ken-Tye
KT
Kumar
Rajiv
R
Hu
Rui
R
Bergey
Earl J
EJ
Schwartz
Stanley A
SA
Prasad
Paras N
PN
D001812:Blood-Brain Barrier; D004298:Dopamine; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000037:antagonists & inhibitors; D016503:Drug Delivery Systems / Q000379:methods*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D020868:Gene Silencing; D006046:Gold; D006801:Humans; D036103:Nanotechnology / Q000379:methods; D043942:Nanotubes; D009474:Neurons / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000628:therapy*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human; D034741:RNA, Small Interfering; D006046:Gold; D048049:Extracellular Signal-Regulated MAP Kinases; D004298:Dopamine