A high lipid-soluble probe for ONOO− recognition in the endoplasmic reticulum and imaging of cerebral ischemia-reperfusion injury

Cerebral ischemia/reperfusion injury (CIRI) is a highly damaging pathological process in stroke. In CIRI, ER stress is the main source of cellular reactive oxygen species (ROS) and significantly contributes to neurological damage. Among ROS, peroxynitrite (ONOO⁻) exhibits potent oxidative and nucleophilic properties. Monitoring ONOO⁻ within the ER is essential for understanding and treating CIRI. However, the lack of probes capable of crossing the blood–brain barrier (BBB) and selectively targeting the ER has hindered progress in this field. To address this challenge, we developed a near-infrared fluorescent probe, , which was designed for both BBB penetration and ER-specific localization. This probe demonstrated high reactivity and superior lipid solubility. The in vitro BBB model assays confirmed its efficient BBB permeability, while imaging studies revealed its ability to dynamically monitor ER-associated ONOO⁻ under various conditions.