Novel Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Superoxide Anion Fluctuations in Ferroptosis-Mediated Epilepsy

Ferroptosis is an iron-regulated, caspase-mediated pathway of cell death that is associated with the excessive aggregation of lipid-reactive oxygen species and is extensively involved in the evolution of many diseases, including epilepsy. The superoxide anion (O2•–), as the primary precursor of ROS, is closely related to ferroptosis-mediated epilepsy. Therefore, it is crucial to establish a highly effective and convenient method for the real-time dynamic monitoring of O2•– during the ferroptosis process in epilepsy for the diagnosis and therapy of ferroptosis-mediated epilepsy. Nevertheless, no probes for detecting O2•– in ferroptosis-mediated epilepsy have been reported. Herein, we systematically conceptualized and developed a novel near-infrared (NIR) fluorescence probe, NIR-FP, for accurately tracking the fluctuation of O2•– in ferroptosis-mediated epilepsy. The probe showed exceptional sensitivity and outstanding selectivity toward O2•–. In addition, the probe has been utilized effectively to bioimage and evaluate endogenous O2•– variations in three types of ferroptosis-mediated epilepsy models (the kainic acid-induced chronic epilepsy model, the pentylenetetrazole-induced acute epilepsy model, and the pilocarpine-induced status epilepticus model). The above applications illustrated that NIR-FP could serve as a reliable and suitable tool for guiding the accurate diagnosis and therapy of ferroptosis-mediated epilepsy.