Development of a hydrogen peroxide fluorescent probe for the rapid discrimination of IDH1 mutant gliomas from the wild-type

Abstract

Isocitrate dehydrogenase (IDH) mutations are common in gliomas, and recent studies have suggested that these mutants have distinct microenvironments characterized by higher levels of reactive oxygen species (ROS) and a higher pH. The identification of IDH mutants is important for the diagnosis, individualized treatment, and clinical prognosis of gliomas. Sanger sequencing and immunohistochemistry are the standard methods for IDH mutation detection. As the mutations have several types, the detection of multiple gene sites and proteins are required, which means high cost and tedious operations. The high levels of ROS observed in mutIDH gliomas have not been used for mutIDH detection. Fluorescent probe-based detection techniques have emerged as a prevalent method to detect diverse analytes in living systems due to their distinctive benefits of simple operation, high sensitivity and selectivity, fast response, and real-time applicability. In the present study, we report the rapid discrimination of mutIDH1 from wild-type gliomas using the novel fluorescent probe BOD-G that varies in its fluorescence response to different levels of H2O2. BOD-G exhibits high sensitivity and selectivity in its turn-on response to H2O2, and its performance improves as the pH increases. The probe exhibits a much stronger fluorescence in IDH1 mutant U87 cells than in wild-type U87MG cells after 5 min. Importantly, BOD-G displays a bright fluorescence when exposed to fresh mutIDH1 human glioma specimens after 15 min but not with wild-type samples. Thus, BOD-G can be used to discriminate mutIDH1 from wild-type human glioma specimens rapidly by simple fluorescent imaging.