ROS-Activatable J-Aggregate Formation of a NIR-II Fluorescent Sensor for Detecting and Imaging Oxidative Stress-Associated Diseases In Vivo

J-aggregates are prized for their unique optical properties in bioimaging, yet the development of activatable sensors based on J-aggregation has been hindered by the scarcity of dyes capable of in situ assembly after a specific biological trigger. To address this, we report an activatable NIR-II fluorescent sensor that enables high-contrast imaging of oxidative stress by leveraging reactive oxygen species (ROS)-triggered J-aggregate formation. We designed and synthesized a heptamethine cyanine dye with a strong propensity for J-aggregation. Its reduced, nonfluorescent hydrocyanine form serves as the probe, which, upon reaction with hydroxyl radicals, regenerates the parent dye. This dye rapidly self-assembles into J-aggregates, emitting a strong NIR-II fluorescence at 1050 nm. The sensor exhibits a nanomolar detection limit for ROS, high specificity, excellent aqueous stability, rapid response, and superb biocompatibility. We successfully demonstrated its utility through in vivo imaging in mouse models of pneumonia and hepatic ischemia–reperfusion injury, where localized fluorescence activation precisely mapped ROS production, enabling deep-tissue imaging. This work underscores the significant potential of J-aggregation-based probes for advanced disease diagnostics and redox biology studies.