title: Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease.
abstract: 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.
authors.affiliation: Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Kwong
authors.forename: Geoffrey
authors.initials: G
authors.lastname: von Maltzahn
authors.forename: Gayathree
authors.initials: G
authors.lastname: Murugappan
authors.forename: Omar
authors.initials: O
authors.lastname: Abudayyeh
authors.forename: Steven
authors.initials: S
authors.lastname: Mo
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Papayannopoulos
authors.forename: Deanna Y
authors.initials: DY
authors.lastname: Sverdlov
authors.forename: Susan B
authors.initials: SB
authors.lastname: Liu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Warren
authors.forename: Yury
authors.initials: Y
authors.lastname: Popov
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D004195:Disease Models, Animal; D006801:Humans; D008103:Liver Cirrhosis / Q000652:urine; D013058:Mass Spectrometry; D051379:Mice; D008991:Monitoring, Physiologic; D053758:Nanoparticles; D009369:Neoplasms / Q000652:urine; D010447:Peptide Hydrolases / Q000652:urine
chemical_list: D015415:Biomarkers; D010447:Peptide Hydrolases