Peeing on a strip of paper could one day reveal signs of cancer and cardiovascular disease. An experimental test uses worm-shaped nanoparticles to spot evidence of tumors and blood clots in mouse urine, researchers report February 24 in the Proceedings of the National Academy of Sciences.
Unlike existing diagnostic tools, the test doesn’t rely on expensive equipment or detection of molecules made by sick people’s bodies. Instead the test looks for synthetic molecules injected into the bloodstream.
“It’s brilliant work — a totally different paradigm for detecting disease,” says analytical chemist Andres Martinezof California Polytechnic State University in San Luis Obispo.
Some diseases send out molecular red flags that are easy to spot in bodily fluids. But cancer and cardiovascular disease don’t reveal such obvious clues. Doctors often need to use biopsies or imaging procedures to spot trouble.
To find a simpler method of disease detection, MIT biomedical engineer Andrew Warren, study leader Sangeeta Bhatia, also of MIT, and colleagues took advantage of a key feature of cancer and thrombosis, a cardiovascular disorder that causes blood clots. Both diseases rely on molecular scissors called protease enzymes. In cancer, these scissors chop up proteins to clear the way for growing tumors. In thrombosis, the scissors help form blood clots.
On their own, the protein-snipping enzymes aren’t useful disease indicators because they’re tough to detect, but combined with nanoparticle worms, the scissors deliver a clear signal. Each worm looks like a tiny fuzzy caterpillar. Tiny balls of rust make up the “body” and short bits of protein “fur” cover the surface. Injected into mice, the worms travel throughout the bloodstream. When they reach a tumor or a blood clot that’s forming, molecular scissors clip off bits of the fur, which flush out of the body in the urine.
Warren’s team detects these bits using paper strips coated with molecules that grab on to the fur fragments. Then the researchers add a solution of gold nanoparticles to the paper. These particles glom onto the fur fragments and paint a reddish line.
“It works exactly the same as a pregnancy test,” Warren says.
He and colleagues tested the diagnostic on mice with blood clots and others growing human colorectal tumors. The urine of both sets of mice produced the telltale reddish line.
“I like this as a potential screening tool,” says Stanford biomedical researcher James Brooks. But he thinks it might be more promising for thrombosis than cancer. The cancer cells the researchers used crank out heaps of scissorlike enzymes, he says. Other tumors might not make as much. Still, he adds, “It’s a very clever technique for detection.”