Mitochondrial-targeting fluorescent probe awakened by nitroreductase for hypoxic imaging and surgical navigation of solid tumors

Abstract

As a typical signal of hypoxia, the up-regulation of nitroreductase (NTR) expression has been widely used to evaluate the anoxic microenvironment of solid tumors. Herein, we propose a near infrared (NIR) fluorescent probe Q-NTR wakened up by NTR in mitochondria. The presence of strong electron-absorbing group nitro can quench fluorescence effectively and provide a sufficiently low background signal. Probe Q-NTR can detect the activity of NTR to evaluate the degree of hypoxia in tumor tissues. Due to its NIR emission, subcellular structure level imaging, and rapid response characteristics, it provides a practical tool for studying NTR activity and hypoxia related biological processes. This sensing scheme has been successfully applied to monitor endogenous NTR activity in subcellular structures (in mitochondria) in anoxic microenvironments and selectively stain cells in anoxic conditions, demonstrated its great potential in early cancer diagnosis. In addition, probe Q-NTR could accurately locate the hypoxic environment, achieving precise navigation during solid tumor resection. In summary, probe Q-NTR will lay the foundation for further research on cell metabolism, tumor metabolism, and solid tumor resection under hypoxic conditions in the future.