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

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

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“…GNRs as a nonviral gene delivery vector have been attracted much interest recently [55][56][57]. Takahashi et al [58] investigated phosphatidylcholine-modified GNRs for releasing plasmid DNA.…”

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“…Encapsulation is the least common approach, as it can be used with only a few types of inorganic nanoparticles, such as calcium phosphate nanoparticles [44,114,134], which can encapsulate the siRNA when added in the synthesis step. Afterwards, these nanoparticles induce the endosomal escape by disruption of the endosome membrane and upon degradation release the siRNA directly in the cytosol (Figure 13) [134].…”