Electrochemiluminescent Detection of hNQO1 and Associated Drug Screening Enabled by Futile Redox Cycle Reaction

Human NAD(P)H: quinone oxidoreductase 1 (hNQO1), a proteinase that engages in detoxification of quinones and capable of activating anti-tumor drugs, has drawn increasing attention as tumor biomarker and drug target. To date, the detection of hNQO1 primarily uses stimulus-responsive probes, involving metabolization of synthetic quinone-functionalized substrates, which however, remain challenging to improve the sensing signal-to-noise ratio, and are lack of sufficient stability. Herein, we report a facile but general way for hNQO1 detection and associated drug screening as well by ECL sensing of the metabolic H₂O₂ enabled by futile redox cycle reaction. Taking advantage of the intrinsic circulatory amplification and the luminol-modified nickel foam electrode, the sensing system exhibited a record-level performance in electrochemiluminescent detection of hNQO1. The same strategy was also successfully applied to rapidly screening hNQO1-directed anti-tumor candidate drugs. The proposed new principle for hNQO1 detection would stimulate ECL as a promising tool that combines diagnostic and drug screening functions for the popularization of proteinases in cancer management.