Monitoring Dynamic Changes of Cellular Membrane GSH During Stroke via an ESIPT-Based Near-Infrared Fluorescent Probe

Stroke, primarily ischemic (85%), results from inadequate blood supply and is worsened by ferroptosis, characterized by free radical generation and lipid peroxidation. Monitoring ferroptosis is essential for understanding its mechanisms and developing treatments. Glutathione (GSH) is a key ferroptosis biomarker, but current probes are limited by short excitation/emission wavelengths, small Stokes shifts, and inability to monitor dynamic GSH changes at the cellular membrane, where ferroptosis plays a crucial role. To address these issues, we developed the PM-Red-GSH, a novel near-infrared (NIR) probe based on the Excited-state intramolecular proton transfer (ESIPT) mechanism. It shows strong NIR emission (715 nm), large Stokes shift (290 nm), and enhanced membrane binding (PCC = 0.95) due to its alkyl group. PM-Red-GSH enables dynamic GSH monitoring in an MCAO mouse model. These findings offer new insights into ferroptosis and stroke treatment.