Ultrasensitive near-infrared fluorescence probe activated by nitroreductase for in vivo hypoxia detection

The fluorescence probe has attracted much attention in the detection of hypoxia-related pathological conditions with unique advantage. However, in vivo imaging the early stages of diseases formation and development remains a great challenge, mainly due to the lack of highly sensitive and specific fluorescence probe. Herein, a high-efficiency near-infrared fluorescence probe YQ-NO2 was synthesized to detect hypoxia via responding to nitroreductase (NTR) in living subjects. In vitro confocal-mediated competitive binding inhibition and flow cytometry analyses indicated YQ-NO2 was of high specificity on hypoxic cells. In vivo near-infrared imaging showed that the probe had the laudable characteristics of a low background inference, fast response and prolonged imaging time in the tumor-bearing mice. Furthermore, it had the property of high affinity and potent permeability, allowing for continuously monitoring cell hypoxia to evaluate longitudinal and dynamic change in the tumor area. Meanwhile, ischemic liver and enteritis sites could be accurately and timely imaged in mice. In addition, it was observed that the fluorescence intensity of the probe in tumor was significantly higher than that in inflammation. The probe has failed to exhibit any bio-toxicity in cells and animals treated with high doses. Ultimately, this near-infrared fluorescence probe will offer an imaging tool for characterizing the hypoxia microenvironment at the tiny lesions in vivo.