Novel BODIPY-based NIR fluorescent probe with appropriate Stokes shift for diagnosis and treatment evaluation of epilepsy via imaging ONOO− fluctuation

Abstract

Epilepsy is a chronic brain disorder characterized by recurrent seizures that has severely threatened human health. Cumulative research achievements uncover that the pathological progression of epilepsy is closely related to peroxynitrite (ONOO⁻). In this work, we first constructed BODIPY dye containing pyridine group and indoline group to make it have the donor-acceptor structure, thus achieving NIR emission wavelength (740 nm) and appropriate Stokes shift (80 nm). Based on the BODIPY dye, the novel probe BDP-NIR-Fa was developed that displayed good specificity, faster response speed (60 s), and high signal to noise ratio (247-fold) for monitoring ONOO. Based on these excellent properties, BDP-NIR-Fa was able to trace endogenous/exogenous ONOO⁻ fluctuations in living cells and mice without interference from other reactive oxygen species. Most importantly, BDP-NIR-Fa could visualize the changes of endogenous ONOO⁻ with remarkable temporal-spatial resolution in KA-induced seizures cell and mice models, that furnishing a potentially forceful tool for diagnosing epilepsy. Finally, BDP-NIR-Fa successfully realized imaging the concentration reduction of ONOO⁻ in epilepsy model during the treatment by an antiepileptic drug. Therefore, the present work provided a reliable approach to investigate the diagnosis and therapy of epilepsy via imaging ONOO⁻ fluctuation.