A nitroreductase responsive and photoactivated fluorescent probe for dual-controlled tumor hypoxia imaging

Tumor hypoxia has great importance in tumor progression and resistance to antitumor therapies. To precisely monitor tumor hypoxia, a controllable hypoxia imaging method is meaningful but still lacking. Herein, we develop a dual-controlled tumor hypoxia probe (TNB) by introducing a nitrophenol group and methyltetrazine group to the boron-dipyrromethene (BODIPY) dye. The fluorescence-quenching group nitrophenol is reduced to aminophenol by upregulated nitroreductase in hypoxic tumors, and the photocage methyltetrazine is cleaved by light irradiation. Hence the fluorescence of TNB is dual-controlled by hypoxia and photoactivation. We first evaluated TNB's potential for controllable hypoxia imaging in solution and tumor cells. The fluorescence of TNB under nitroreductase incubation and photoactivation increased more than 60 fold over that which was untreated or only treated with nitroreductase. Furthermore, results validate that TNB possesses photo-controllable activation features in tumor sections. We believe that the probe design based on enzyme and photoactivation responsiveness provides potential for spatiotemporal detection of other biomarkers.