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.