Biomarkers are increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous biomolecules. Here I describe the development of “synthetic biomarkers” comprising protease-sensitive nanoparticles that perform three functions following administration: they target sites of disease, sense dysregulated protease activities, and release reporters into the host urine as indicators of disease. These urinary reporters are mass-encoded to allow multiplexed analysis by mass spectrometry, or functionalized with capture ligands to allow detection by low-cost paper tests in global health settings. By engineering nanoparticles to sense different proteases, I show that synthetic biomarkers may be used to noninvasively monitor liver fibrosis and reversal, detect dangerous pulmonary blood clots and detect cancer earlier compared to blood biomarkers. Synthetic biomarkers have the potential to significantly expand our repertoire of diagnostic nanomedicines, and may allow systems-level analysis of multi-enzymatic networks in health and disease.
https://mediaspace.gatech.edu/media/kwong/1_ur59cj60