Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons
- Adela C. Bonoiua,1,
- Supriya D. Mahajanb,1,
- Hong Dinga,
- Indrajit Roya,
- Ken-Tye Yonga,
- Rajiv Kumara,
- Rui Hua,
- Earl J. Bergeya,
- Stanley A. Schwartzb and
- Paras N. Prasada,2
- aInstitute for Lasers Photonics and Biophotonics, The State University of New York, Buffalo, NY 14260; and
- bDepartment of Medicine, Division of Allergy, Immunology, and Rheumatology, The State University of New York, Buffalo General Hospital, Buffalo, NY 14203
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↵1These authors contributed equally to this work.
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Communicated by Kenneth B. Eisenthal, Columbia University, New York, NY, February 18, 2009 (received for review October 21, 2008)
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.
Footnotes
- 2To whom correspondence should be addressed. E-mail: pnprasad{at}buffalo.edu
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Author contributions: A.C.B., S.D.M., I.R., E.J.B., S.A.S., and P.N.P. designed research; A.C.B., S.D.M., R.K., and R.H. performed research; H.D., K.-T.Y., R.K., and R.H. contributed new reagents/analytic tools; A.C.B., S.D.M., H.D., I.R., K.-T.Y., E.J.B., S.A.S., and P.N.P. analyzed data; and A.C.B., S.D.M., and P.N.P. wrote the paper.
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The authors declare no conflict of interest.
