A near-infrared frequency upconversion probe for nitroreductase detection and hypoxia tumor in vivo imaging

Nitroreductase (NTR) acts as a detective enzyme that can be used to judge the hypoxic level of solid tumors. To date, only a few optical probes can effectively and selectively monitor NTR in vivo. Therefore, it is important to develop an ideal probe with near-infrared (NIR) excitation and emission for NTR detection and imaging. In this study, we report a NIR frequency upconversion luminescence (FUCL) probe (Cy7-NO2) based on a cyanine structure decorated with an aromatic nitro group to detect NTR in vivo. Cy7-NO2 not only was excited at 850 nm and emitted at 790 nm, but also showed a fast and selective response to NTR. Docking calculations revealed that NTR was able to form hydrogen bonds with Cy7-NO2 and underwent an enzyme-catalyzed reduction reaction. Compared with absorption and the Stokes emission methods, FUCL method exhibited a lower detection limit (3.4 ng mL(-1)). In addition, Cy7-NO2 was used for FUCL bioimaging of NTR in living cells and mice. All of these results proved that Cy7-NO2 as a FUCL probe supplies a new method for biodetection and bioimaging of NTR in vitro and in vivo.