A hydrogen peroxide-responsive near-infrared fluorescent probe for visualizing redox-associated signals in acute colitis and gastrointestinal tumor models and monitoring treatment-related changes.

Inflammatory bowel disease and gastrointestinal tumors are accompanied by redox imbalance, yet noninvasive tools for visualizing hydrogen peroxide-associated redox changes and following responses to intervention remain limited. This study aimed to develop and preclinically evaluate HD-YSY, a boronate-masked hemicyanine compound activated by hydrogen peroxide. High-performance liquid chromatography supported formation of the deprotected fluorophore HD. Under the stated solution conditions, the probe produced first-window near-infrared emission at 760 nm under 670 nm excitation, showed a rapid fluorescence increase during a 100 s observation interval, was linear from 0 to 10 μM hydrogen peroxide, yielded a calculated detection limit of 0.15 μM, and retained a pronounced response from pH 6.0 to 9.0. The activated fluorescent product showed preferential mitochondrial localization in murine foregastric carcinoma cells (Pearson r = 0.90 with Mito-Tracker Green versus 0.65 with Lyso-Tracker Green). Under matched acquisition conditions, fluorescence increased across increasing dextran sulfate sodium concentrations in an acute colitis model, differed between 3 T3 fibroblast and SW480 colorectal carcinoma xenograft settings, and changed during pharmacological intervention. These signals are interpreted as semiquantitative, hydrogen peroxide-associated redox readouts rather than absolute intracellular or in vivo hydrogen peroxide concentrations. The principal advance is the integration of solution, cellular, acute-colitis, xenograft, and treatment-monitoring experiments on one platform; the probe itself is not therapeutic, and further mechanistic, pharmacokinetic, and disease-model validation is required.