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

Abstract

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.

Activatable Dual-Optical Molecular Probe for Bioimaging Superoxide Anion in Epilepsy

“…Mice were injected intraperitoneally with saline (0.2 mL) every other day in the control group. While in the epileptic group, PTZ was administered intraperitoneally to mice every other day. , In the treatment group, epileptic mice were intraperitoneally injected using N -acetylcysteine (NAC) (20 mg/kg) once a day for 5 days.…”

“…Following each administration, the behavior and seizure activity of the mice were continuously monitored for 60 min. The seizure activity of the mice was classified and scored on a modified Racine Scale. , The PTZ ignition epilepsy model was successfully induced when five consecutive seizure scores reached a threshold of ≥2. The behavior of the mice was monitored with a video camera throughout the experiment.…”

“…The design and synthesis of the probe directly affect the final imaging effect. To date, some fluorescent probes have been reported for the detection of O 2 •– in epilepsy. , Few chemiluminescent probes have been in detecting O 2 •– in vivo (Table S1). − However, no probe has been reported that can simultaneously switch on dual optical modes (FL and CL) in response to the O 2 •– in epilepsy.…”

Tri-mode Responses to Reactive Oxygen Species In Vivo by Chiral Vanadium-Based Nanoparticles

“…However, there is a paucity of high-sensitivity biological sensors because the associated preparation conditions are often complex, costly, and potentially toxic and may suffer from stability issues. Traditional techniques for monitoring ROS, such as electron paramagnetic resonance, fluorescence, − chemiluminescence, , and electrochemical analysis, − typically have several limitations, including poor stability, low sensitivity, and cumbersome operation . Therefore, it is of utmost importance to develop new methods with high sensitivity and superior biocompatibility to measure ROS in complex biological environments.…”

A Sequentially Activated Probe for Imaging of Superoxide Anion and Peroxynitrite in PC12 Cells under Oxidative Stress

“…Given the high reactivity and short lifespan of O 2 ·– and ONOO – , conventional histological and biochemical analysis techniques lack the ability to assess their dynamic changes within cells or in vivo in real-time. Fluorescence imaging offers a crucial tool for the noninvasive investigation of biological processes in cells and transparent organisms due to its superior spatiotemporal resolution, sensitivity, and ability to detect targets in situ and/or in real-time within complex biosystems − While numerous fluorescent probes have been developed for the specific detection of O 2 ·– − or ONOO – , − few have been able to simultaneously visualize both species in vitro and in vivo . Although it is possible to use a single fluorescent probe for O 2 ·– and another for ONOO – simultaneously, data interpretation becomes challenging due to their different uptake, distribution, and metabolism profiles.…”