A nitroreductase-sensitive near-IR fluorescent biosensor for detecting tumor hypoxia in vivo

Tumor cells have high metabolic demands, leading to increased oxygen consumption and further exacerbating hypoxia, which has been regarded as a characteristic feature of solid tumors and plays a significant role in tumor growth, resistance to therapy, and overall treatment outcomes. Hypoxia-specific sensing probes are currently in urgent need to provide valuable information for tumor detection and monitoring. In this work, we developed a new near-IR fluorescence-emitting biosensor with a high fluorescence quantum yield for hypoxia detection in tumor tissues. In the presence of nitroreductase enzyme under tumor hypoxia, the nitro group of the biosensor molecule is converted into an amino group, and the resulting compound turns itself into a nonfluorescent dye through a self-immolating process, thus turning off the fluorescence emission of the biosensor. The fluorescence change of the biosensor in response to nitroreductase is sensitive and selective and is not influenced by the presence of other physiologically important species. In the in vitro and in vivo bioimaging experiments, the biosensor demonstrated high efficiency in detecting hypoxia and the capability of distinguishing solid tumors of different sizes, indicating its potential applications in tumor diagnosis and progression monitoring.