Researchers Create DNA-Based Sensors for Nano-Tongues and Nano-Noses

Researchers from Rice University's Center for Biological and Environmental Nanotechnology (CBEN) have developed a "smart" beacon hundreds of times smaller than a human cell that is programmed to light up only when activated by specific proteases. Altered expression of particular proteases is a common hallmark of cancer, atherosclerosis, and many other diseases.

According to the researchers, targeted nanostructures – including

Illustration of “smart” probe concept.  Quantum dot surrounded by gold nanoparticles connected via degradable peptides (left).  Cleavage of peptide separates gold nanoparticles (middle) enabling quantum dots to glow brightly (right).

quantum dots – used for molecular imaging have never been able to adequately solve the problem of clearly distinguishing between the “cancer is here” signal and the background light, which arises from nanostructures not specifically bound to their molecular targets.

Rice's technology solves this longstanding problem by using emissive nanoparticles called quantum dots that give off light in the near-infrared (NIR), a rare portion of the spectrum that has no background component in biomedical imaging. Near-infrared light also passes harmlessly through skin, muscle and cartilage, so the new probes could alert doctors to tumors and other diseases sites deep in the body without 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 to inhibit luminescence. The tether, a peptide sequence measuring only a few nanometers, or billionths of a meter, holds the gold close enough to prevent the quantum dot from giving off its light.

In their test system, the Rice team used a peptide tether that is cleaved by the enzyme collagenase. The researchers first showed that luminescence of the quantum dots was cut by more than 70 percent when they were attached to the gold particles. They remained dark until the nanostructures were exposed to collagenase after which the luminescence steadily returned.

Ultimately, the researchers hope to pair a series of quantum dots, each with a unique NIR optical signature, to an index of linker proteases.

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