Synthetic Biomarkers Monitor Disease

If you can’t find natural biomarkers to monitor a disease, the next best option may be to just make them yourself. A team of researchers led by Sangeeta N. Bhatia of MIT has done just that. They made synthetic biomarkers by attaching mass-encoded peptides to polyethylene glycol-coated iron oxide nanoparticles (Nat. Biotechnol., DOI: 10.1038/nbt.2464). The peptides, which are substrates for disease-associated proteases, are tagged with isobaric reporters, which have the same overall mass but produce distinctive fragment ions during mass spectrometry. The proteases cleave the peptides and release the reporters, which can be collected in urine. The isobaric tags make it easy to collect the reporters at a single mass and then differentiate them by their fragmentation spectra. The researchers used the reporters in mouse models for monitoring liver fibrosis, a wound-healing response to chronic liver injury, and for early detection of colorectal cancer. The strategy could be adapted for other diseases by using other scaffolds, targeting other enzyme families, and using other reporters.