Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease
| Autor: | Sangeeta N. Bhatia, Andrew Warren, Gabriel A. Kwong, Geoffrey von Maltzahn, Deanna Y. Sverdlov, Steven Mo, Detlef Schuppan, Yury Popov, Gayathree Murugappan, Omar O. Abudayyeh, Susan B. Liu, Ioannis A. Papayannopoulos |
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| Rok vydání: | 2011 |
| Předmět: |
Liver Cirrhosis
Urinary system Biomedical Engineering Early detection Bioengineering Computational biology Disease Biology 010402 general chemistry 01 natural sciences Applied Microbiology and Biotechnology Mass Spectrometry Article 03 medical and health sciences Mice In vivo Neoplasms medicine Animals Humans Amino Acid Sequence Biomarker discovery 030304 developmental biology Monitoring Physiologic 0303 health sciences Cancer medicine.disease 3. Good health 0104 chemical sciences Disease Models Animal Blood biomarkers Immunology Molecular Medicine Nanoparticles Core biopsy Biomarkers Biotechnology Peptide Hydrolases |
| Zdroj: | Nature biotechnology |
| ISSN: | 1546-1696 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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