A sulfonate-modified cyanine-based photoacoustic probe for selective detection of hydroxyl radicals in diabetic liver injury.

Hydroxyl radicals (•OH) play a critical role in oxidative stress-related diseases, yet their real-time detection in vivo remains challenging. We developed a hydroxyl radical-responsive photoacoustic probe (OHP) by modifying IR780-SO3H with enhanced hydrophilicity (logP = -1.051) for improved biodistribution. Structural characterization confirmed the selective reduction of the conjugated system, while in vitro studies demonstrated OHP's selective and linear response to •OH with minimal interference from other ROS/RNS. In diabetic mice, OHP enabled dynamic monitoring of hepatic •OH levels, revealing elevated oxidative stress that was attenuated by metformin treatment. Ex vivo fluorescence imaging and histopathology validated the imaging results, showing strong correlation with disease severity. Biosafety assessments confirmed negligible cytotoxicity in cells and mice. OHP represents a sensitive, selective, and biocompatible tool for non-invasive •OH detection, offering potential for studying oxidative stress and therapeutic interventions.