Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 14, Pages 5546-5550Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0901715106
Keywords
DARPP-32; dark field imaging; surface plasmon resonance; nanoplexes; blood-brain barrier
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Funding
- National Cancer Institute [CA119397, CA104492]
- Kaleida Health Cameron Troup Foundation
- Oishei Foundation
- Chemistry and Life Sciences Division of the Air Force Office of Scientific Research
- Center of Excellence in Bioinformatics and Life Sciences
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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.
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