FRET Luminescent Probe for the Ratiometric Imaging of Peroxynitrite in Rat Brain Models of Epilepsy-Based on Organic Dye-Conjugated Iridium(III) Complex.

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures globally, imposing a substantial burden on patients and their families. The pathological role of peroxynitrite (ONOO-), which can trigger oxidative stress, inflammation, and neuronal hyperexcitability, is critical in epilepsy. However, the development of reliable, in situ, and real-time optical imaging tools to detect ONOO- in the brain encounters some challenges related to the depth of tissue penetration, background interference, optical bleaching, and spectral overlapping. To address these limitations, we present Ir-CBM, a new one-photon and two-photon excitable and long-lived ratiometric luminescent probe designed specifically for precise detection of ONOO- in epilepsy-based on the Förster resonance energy transfer mechanism by combining an iridium(III) complex with an organic fluorophore. Ir-CBM possesses the advantages of rapid response, one-/two-photon excitation, and ratiometric luminescent imaging for monitoring the cellular levels of ONOO- and evaluating the effects of different therapeutic drugs on ONOO- in the brain of an epilepsy model rat. The development and utilization of Ir-CBM offer valuable insights into the design of ratiometric luminescent probes. Furthermore, Ir-CBM serves as a rapid imaging and screening tool for antiepileptic drugs, thereby accelerating the exploration of novel antiepileptic drug screening and improving preventive and therapeutic strategies in epilepsy research.