HOUSTON, Aug. 1, 2005 -- Researchers from Rice University's Center forBiological and Environmental Nanotechnology (CBEN) have developed a"smart" beacon hundreds of times smaller than a human cell that isprogrammed to light up only when activated by specific proteases.Altered expression of particular proteases is a common hallmark ofcancer, atherosclerosis, and many other diseases.
In the September issue of the journal Biochemical and Biophysical Research Communications,lead authors Jennifer West, the Isabel C. Cameron Professor ofBioengineering and director of CBEN's biological research program, andRebekah Drezek, the Stanley C. Moore Assistant Professor ofBioengineering and assistant professor of electrical and computerengineering, describe development of a new nanoprobe for visualizationof proteolytic activity in vivo.
"The idea is to develop a 'smart' nanostructure that is dark inits original state but lights up very brightly in the presence ofenzymatic activity associated with a particular disease process," saidWest. "Other groups have used targeted nanostructures including quantumdots for molecular imaging, but they have never been able to adequatelysolve the problem of clearly distinguishing between the 'cancer ishere' signal and the background light which arises from nanostructuresnot specifically bound to their molecular targets."
Rice's technology solves this longstanding problem by usingemissive nanoparticles called quantum dots that give off light in thenear-infrared (NIR), a rare portion of the spectrum that has nobackground component in biomedical imaging. Near-infrared light alsopasses harmlessly through skin, muscle and cartilage, so the new probescould alert doctors to tumors and other diseases sites deep in the bodywithout the need for a biopsy or invasive surgery.
The probe's design makes use of a technique called "quenching"that involves tethering a gold nanoparticle to the quantum dot toinhibit luminescence. The tether, a peptide sequence measuring only afew nanometers, or billionths of a meter, holds the gold close enoughto prevent the quantum dot from giving off its light.
In their test system, the Rice team used a peptide tether thatis cleaved by the enzyme collagenase. The researchers first showed thatluminescence of the quantum dots was cut by more than 70 percent whenthey were attached to the gold particles. They remained dark until thenanostructures were exposed to collagenase after which the luminescencesteadily returned.
Ultimately, the researchers hope to pair a series of quantumdots, each with a unique NIR optical signature, to an index of linkerproteases.
"There is currently a critical need for methods tosimultaneously image the activity of multiple proteases in vivo," saidDrezek. "This is important not only for early detection of severaldiseases, but perhaps more significantly, in understanding andmonitoring the efficacy of therapeutic interventions, including thegrowing class of drugs that act as protease inhibitors. What isparticularly powerful about the protease imaging probes described inthis study is the combination of the contrast enhancement achievablethrough an activateable probe with the imaging advantages provided bythe brightness, photostability, and tunability of quantum dots."
CBEN research is funded by the National Science Foundation.
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