Construction of nitroreductase-responsive near-infrared composite nanoprobe and its application in tumor hypoxia imaging

Hypoxia is an important feature in the development of solid tumors. Nitroreductase (NTR) is closely related to the level of hypoxia, thus NTR-responsive fluorescent probes with high selectivity and sensitivity will help to evaluate the degree of hypoxia and guide personalized treatment. In this study, a near-infrared (NIR) NTR-activated composite nanoprobe 780-pNBC@MP-B was developed for tumor hypoxia imaging. The nanoprobe has a mesoporous organosilicon nanostructure functionalized with PEG for in vivo long circulation, and encapsulates a NIR molecular probe 780-pNBC for NTR imaging, which can exhibit responsive degradation to glutathione (GSH) attributed to the disulfide bond in the nanocarrier structure. Benefiting from the hydrophilic nanocarrier, 780-pNBC@MP-B with good water dispersibility and photostability was successfully applied to visualize NTR in hypoxic cells and tumor-bearing mice. Therefore, this work provides a new tool for tumor hypoxia detection and expands the new application of mesoporous silica in the field of enzyme probes.