Rational design of a nitroreductase-activatable two-photon fluorescent probe for hypoxia imaging in cell and in vivo

Tumor resistance is a huge challenge for tumor treatment, which may lead to tumor treatment failure. Relieving tumor resistance and improving efficacy are long-term goals for tumor treatment. Nitroreductase (NTR) is an endogenous enzyme that highly expressed in hypoxia tumors. Herein, we develop a NTR-activatable fluorescent probe, TP-NO2, for NTR detection during tumor treatment. TP-NO2 with simple synthesis steps and high yield can qualitatively and quantitatively detect NTR in a wide range (0 - 20 mu g/mL) with a detection limit of 26 ng/mL. The probe has been successfully applied for NTR detection in cells under simulated hypoxia conditions. Hyperbaric oxygen (HBO) can alleviate tumor hypoxia and reduce NTR concentration. We pre-evaluate the effect of tumor treatment by NTR imaging. And the results demonstrate that HBO-assistant chemotherapy can effectively treat tumor cells. We further apply TP-NO2 for NTR detection in A549 and cis-dichlorodiamineplatinum(II) (DDP)-resistant A549 (A549/DDP) xenograft nude mice, and we choose NTR as an indicator to pre-evaluate the treatment efficacy of malignant tumors. With the adjuvant therapy of HBO, chemotherapeutic drugs gemcitabine and carboplatin can effectively treat A549 and A549/DDP xenograft. These applications provide us a novel perspective for NTR imaging.