A novel GSH-activable theranostic probe containing kinase inhibitor for synergistic treatment and selective imaging of tumor cells

Abstract

Theranostic probe is becoming a powerful tool for diagnosis and treatment of cancer. Although some theranostic probes have been successfully developed, there is still a great room for improvement in sensitive diagnosis and efficient treatment. Herein, we developed a novel GSH-activable theranostic probe NC-G, which uses 1,8-naphthalimide-4-sulfonamide as a fluorescence imaging group and crizotinib as a highly toxic kinase inhibitor to tumor cells. The probe not only has high sensitivity (DL = 74 nM) and specificity, but also can detect GSH sensitively in cells and zebrafish. In addition, probe NC-G can not only show more obvious fluorescence in tumor cells to achieve sensitive diagnosis of tumor cells, but also release the inhibitor crizotinib to achieve high toxicity to tumor cells. It is worth noting that the consumption of GSH can cause oxidative stress response of cells and the release of SO₂ can induce cell apoptosis during the recognition process of the probe and GSH. Thus, the synergistic effect of crizotinib, GSH depletion, and SO₂ release provides a highly effective therapeutic feature for tumor cells. Therefore, probe NC-G can serve as an excellent theranostic probe for sensitive imaging and highly effective treatment of tumor cells.

Keywords: Crizotinib; Fluorescent probe; Glutathione; Kinase inhibitor; Theranostic probe.