Hypoxia is the condition of oxygen deficiency in tissues. It is associated with many diseases such as solid tumor, ischemia etc. Under hypoxic condition, several redox species including a nitro-substrate reducing enzyme nitroreductase (NTR) are elevated in cell. Based on this fact, we intended to assess the hypoxia susceptibility of different organ tissues by analyzing their activity of nitroreductase. However, a suitable probe for such an application needs to meet several criteria. Such as ratiometric signaling (to avoid concentration-dependent signal perturbation), two-photon activity (to obtain deep tissue imaging), NIR emission (to avoid auto-fluorescence), and pH independent emission behavior (to avoid signal perturbation due to different pH of organs). To address these problems we have developed an NIR emitting two-photon ratiometric probe, which outperforms other NTR probes reported till date. Among the organs we investigated (mouse lung, heart, spleen, kidney, and liver), the kidney showed significantly higher susceptibility to hypoxia, which is due to the critical function of the medulla, but not the cortex. The probe offers an ideal tool for studying the nitroreductase activity and, moreover, hypoxia-associated biological processes.

NIR emissive probe offering two-photon ratiometric imaging of nitroreductase for studying organ hypoxia susceptibility

ACS Spring 2022

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