Visualizing nitroreductase activity in living cells and tissues under hypoxia and hepatic inflammation

Detecting nitroreductase (NTR) activity in hypoxic cells and tissues in situ represents an important step toward accurate delineation of hypoxic disease loci. However, it remains challenging to develop fluorescent probes with the necessary attributes of selectivity, sensitivity, precise targeting and aqueous solubility. Herein, two kinds of fluorescent probes (NNP and cRGD-NNP) built on a 2-nitroimidazole sensing platform were synthesized for the detection of NTR activity in cell and in vivo models of hypoxia. In the presence of NADH, NNP displayed high selectivity for NTR, a strong fluorescence enhancement (108 fold), and a low detection limit (3.6 ng mL(-1)). Benefiting from the hydrophilic structure and tumor-targeting properties of the cRGD cyclopeptide group, the probe cRGD-NNP efficiently detected NTR activity in MCF cancer cells under hypoxia. In addition, the liposome-encapsulated probe was successfully applied to visualize NTR during liver inflammation in mice.

Automated summary

In this study, two fluorescent probes were successfully synthesized for the detection of NTR activity in cell and in vivo models. One probe showed high selectivity for NTR, strong fluorescence enhancement, and low detection limit in the presence of NADH. The other tumor-targeting probe efficiently detected NTR activity in cancer cells. The liposome-encapsulated probe was successfully applied to visualize NTR during liver inflammation in mice.