Synthetic Biomarker Design by Using Analyte-Responsive Acetaminophen

The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy that uses analyte-responsive acetaminophen (APAP) to expand the catalogue of analytes available for synthetic biomarker development. As proof-of-concept, we designed hydrogen peroxide (H2O2)-responsive APAP (HR-APAP) and succeeded in H2O2 detection with cellular and animal experiments. In fact, for blood samples following HR-APAP injection, we demonstrated that the plasma concentration ratio [APAP+APAP conjugates]/[HR-APAP] accurately reflects in vivo differences in H2O2 levels. We anticipate that our practical methodology will be broadly useful for the preparation of various synthetic biomarkers.