A high-performance enzyme-activated near-infrared probe for the sensing and tracking of tumor-related NQO1 in cells and in vivo

High-performance near-infrared (NIR) probes can achieve rapid and effective imaging and tracking of tumor biomarkers, which have attracted extensive attention in tumor visualization and early diagnosis. Fast response speed and high contrast fluorogenic enhancement are important criteria for high-performance imaging probes. Here, by introducing two hydrophilic sulfonates into the probe structure, we designed and optimized a new NAD(P)H:quinone oxidoreductase-1 (NQO1) activated NIR fluorogenic probe (S-QCy7-NQO1) for sensitive detection and evaluation of NQO1 activity in cell and tumor xenografts mice. The catalytic reduction activity of NQO1 quickly eliminated the highly selective quinone trigger, and then the probe S-QCy7-NQO1 was converted into S-QCy7 with an extended conjugated system, resulting in a 245-fold increase in NIR fluorescence, 4.9 times higher than that of QCy7-NQO1 without sulfonates. The introduction of two hydrophilic sulfonates also endows S-QCy7-NQO1 a fast response to NQO1, which is 2 times faster than QCy7-NQO1. The probe S-QCy7-NQO1 showed remarkable responsiveness, sensitivity and optical performance to NQO1 under physiological conditions, allowing the detection of endogenous NQO1 activity in living cells with an ultra-high positive-to-negative ratio (108-fold). Notably, with the improved responsiveness and optical properties, it was further applied to high-contrast imaging of tumor-bearing mice, achieving the maximum fluorescence response within 10 min. On this basis, S-QCy7-NQO1 can be a potentially practical tool for early cancer diagnosis characterized by elevated NOQ1 levels. • A high-performance NQO1-activated NIR fluorogenic probeS-QCy7-NQO1 is reported. • Rapid response, high sensitivity and selectivity. • Increase in hydrophilic properties can significantly improve the response efficiency and fluorescence of probe. • Detection of endogenous NQO1 activity in living cells and high-contrast imaging of tumor-bearing mice.