These nanoparticles created by MIT engineers can act as synthetic biomarkers for disease. The particles (brown) are coated with peptides (blue) that are cleaved by enzymes (green) found at the disease site. The peptides then accumulate in the urine, where they can be detected using mass spectrometry. Image: Justin H. Lo
Scientists have been trying to spot biomarkers in bodily fluids in a search for cancer that can be well compared to looking for a few tiny needles in a huge haystack. Typically this requires incredibly sensitive microfluidic devices and other specialized equipment. To get around this problem, researchers from MIT and Harvard have come up with nanoparticles that they call “synthetic biomarkers” that detect cancer biomarkers and produce large quantities of their own that are much easier to spot.
The researchers were able to detect early colorectal cancer in mice and monitored the progression of liver fibrosis by detecting the newly produced biomarkers in urine using traditional mass spectrometry.
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Cancer cells often produce large quantities of proteases known as MMPs. These proteases help cancer cells escape their original locations and spread uncontrollably by cutting through proteins of the extracellular matrix, which normally holds cells in place.
The researchers coated their nanoparticles with peptides (short protein fragments) targeted by several of the MMP proteases. The treated nanoparticles accumulate at tumor sites, making their way through the leaky blood vessels that typically surround tumors. There, the proteases cleave hundreds of peptides from the nanoparticles, releasing them into the bloodstream.
The peptides rapidly accumulate in the kidneys and are excreted in the urine, where they can be detected using mass spectrometry.
To make the biomarker readings as precise as possible, the researchers designed their particles to express 10 different peptides, each of which is cleaved by a different one of the dozens of MMP proteases. Each of these peptides is a different size, making it possible to distinguish them with mass spectrometry. This should allow researchers to identify distinct signatures associated with different types of tumors.
Press release: New technology may enable earlier cancer diagnosis
Study in Nature Biotechnology: Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease
