Abstract
Nitroreductase (NTR) is a highly expressed endogenous enzyme in hypoxic tumor cells, which is associated with the hypoxic degree in tumors. Therefore, it is particularly important to develop low-toxicity and high-sensitivity fluorescent probes for NTR. Herein, we report an NTR-activated near-infrared probe with good selectivity and sensitivity. More importantly, the background fluorescence signal is effectively reduced due to the quenching effect of nitro group as well as the spironolactone (ring-closed) form of rhodamine moiety. Upon reaction with NTR, the probe exhibits a remarkable fluorescence off-on response at 740 nm (about 32-fold intensity enhancement), with an extremely low detection limit of 1.09 ng/mL. Moreover, the probe is able to target mitochondria. With this probe, we have achieved the visualization of NTR overexpression in hypoxic cancer cells, as well as in hypoxic tumors in vivo as revealed in the tumor-bearing mouse model. By using this probe, some essential information may be revealed about hypoxia-relevant diseases.
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