Gold nanorods can deliver silencing RNA into neurons to inactivate the signalling pathways involved in drug addiction
Drug addiction involves the activation of the dopaminergic signalling pathway in the brain. One way to combat this is to switch off this 'trigger' using silencing RNA (siRNA). Researchers at the State University of New York at Buffalo now show that siRNA complexed with gold nanorods can enter neurons and reduce the expression of key proteins in the signalling pathway, offering a potential therapy for drug addiction.
Paras Prasad and co-workers1 complexed siRNA with gold nanorods and delivered them to neurons in vitro and measured the expression of three key genes that modulate one another in a cascade-like fashion — DARPP-32, ERK and PP-1. The siRNA–gold complex silenced the expression of DARPP-32 (the central molecular 'trigger'), ERK and PP-1 (two key molecules downstream of the signalling pathway) more effectively than when siRNA was complexed to a commercial carrier. Moreover, the siRNA-gold complex was able to cross an in vitro model blood–brain barrier and continued to retain its function. Treating morphine-treated neurons with this complex showed similar suppression of these three genes.
Although the siRNA-gold complex could silence the three key genes effectively in vitro without observable toxic effects, several challenges in vivo still remain. Nevertheless, siRNA therapy combined with traditional psychological and sociological methods may potentially be an effective approach to treat drug addiction.
References
Bonoiu, A. C. et al. Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons. Proc. Natl Acad. Sci. USA 10.1073/pnas.0901715106 (2009).
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Chun, A. Delivering the message. Nature Nanotech (2009). https://doi.org/10.1038/nnano.2009.109
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DOI: https://doi.org/10.1038/nnano.2009.109