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.