Journal
NATURE BIOTECHNOLOGY
Volume 31, Issue 1, Pages 63-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.2464
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Funding
- US National Institutes of Health (Bioengineering Research Partnership) [R01 CA124427]
- Kathy and Curt Marble Cancer Research Fund
- US National Institutes of Health [U19 AI066313, 1R21 DK075857]
- Ruth L. Kirschstein National Research Service Award [F32CA159496-01]
- NATIONAL CANCER INSTITUTE [R01CA124427, F32CA159496, P30CA014051] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI066313] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK076873, R21DK075857] Funding Source: NIH RePORTER
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Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that these agents can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and substantially improve early detection of cancer compared with current clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and point-of-care diagnostics.
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