April 24, 2006
Gold Nanoparticles Screen for Novel DNA Binding Drugs
Given that cancer is ultimately a disease of altered gene function, it should come as no surprise that cancer researchers are attempting to develop various methods of turning off genes that are not working properly. One such approach involves using specially designed nucleic acids known as triplex binders that attach themselves to the DNA double helix at the site of the malfunctioning genes, which has the net effect of turning off those genes. Now, thanks to nanotechnology, researchers have a sorely needed technique for rapidly screening potential triplex binders.
Chad Mirkin, Ph.D., principal investigator of the Nanomaterials for Cancer Diagnostics and Therapeutics Center of Cancer Nanotechnology Excellence at Northwestern University, and his colleagues have used gold nanoparticles to create their new screening technology. The assay consists of two sets of gold nanoparticle-DNA constructs and a free strand of DNA. One of the nanoparticles will always bind to the free piece of DNA, but the second nanoparticle only binds to the free DNA in the presence of a triplex binder.
In the absence of a triplex binder, the assay mixture is red in color, but the mixture turns blue when a triplex binder is added to the mixture. This easily measured color shift results from electronic interactions that occur between two gold nanoparticles brought close to one another within the DNA triplex. The amount of color change, which again is easily measured using a standard spectrophotometer, correlates with how effective a triplex binder is at forming a triple helix structure. The investigators note that this assay can be adapted easily for use in high-throughput screening systems.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “A gold nanoparticle based approach for screening triplex DNA binders.” An abstract of this paper is available through PubMed.