Electrochemiluminescent detection of hNQO1 and associated drug screening enabled by futile redox cycle reaction

Abstract

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. Despite significant advances, the detection of hNQO1 up to now primarily relies on stimulus-responsive probes involving metabolization of a complicated synthetic quinone-functionalized probe, which, however, remains challenging to improve the sensing sensitivity, and are lack of sufficient stability. Herein, we report a highly sensitive electrochemiluminescent detection of hNQO1 and associated drug screening by straightforward sensing of the metabolin, enabled by a futile redox cycle reaction. Thanks to the intrinsic circulatory amplification and the luminol-modified nickel foam electrode, the electrochemiluminescent (ECL) sensor exhibited a record-level detection limit (10 ng/mL) and SNR (∼460) for hNQO1. The same format was also successfully applied to rapidly ranking hNQO1-directed anti-tumor drugs down to several-ten minutes. This new strategy would open a new era for hNQO1 detection with uncompromised high performance and also stimulate ECL as a promising tool that combines both diagnostic and drug screening functions for the popularization of proteinases in cancer management in a future application.