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

Ferroptosis is an iron-regulated, caspase-mediated pathwayof celldeath that is associated with the excessive aggregation of lipid-reactiveoxygen species and is extensively involved in the evolution of manydiseases, including epilepsy. The superoxide anion (O-2 (& BULL;-)), as the primary precursor of ROS, is closelyrelated to ferroptosis-mediated epilepsy. Therefore, it is crucialto establish a highly effective and convenient method for the real-timedynamic monitoring of O-2 (& BULL;-) duringthe ferroptosis process in epilepsy for the diagnosis and therapyof ferroptosis-mediated epilepsy. Nevertheless, no probes for detectingO(2) (& BULL;-) in ferroptosis-mediated epilepsyhave been reported. Herein, we systematically conceptualized and developeda novel near-infrared (NIR) fluorescence probe, NIR-FP, for accurately tracking the fluctuation of O-2 (& BULL;-) in ferroptosis-mediated epilepsy. The probe showed exceptional sensitivityand outstanding selectivity toward O-2 (& BULL;-). In addition, the probe has been utilized effectively to bioimageand evaluate endogenous O-2 (& BULL;-) variationsin three types of ferroptosis-mediated epilepsy models (the kainicacid-induced chronic epilepsy model, the pentylenetetrazole-inducedacute epilepsy model, and the pilocarpine-induced status epilepticusmodel). The above applications illustrated that NIR-FP could serve as a reliable and suitable tool for guiding the accuratediagnosis and therapy of ferroptosis-mediated epilepsy.