Dual-Locked Near-Infrared Hemicyanine Probe toward ATP and HClO for Improved Inflammatory Bowel Disease Diagnosis

Abstract Inflammatory bowel disease (IBD) is pathologically characterized by oxidative stress and disrupted energy metabolism, which is closely related to the overproduction of ATP and hypochlorite (ClO–). However, fluorescent probes capable of simultaneous detection of ATP and ClO– remain scarce. Herein, we report an ATP/ClO–-activatable hemicyanine-based fluorescent probe, AClO–CHcy, for accurate diagnosis of IBD. This dual-locked probe features two independent recognition units: a cyclization switch for ATP sensing and a thiocarbamate group responsible for ClO– response, displaying intense near-infrared (NIR) fluorescence at 706 nm only upon dual stimulation. AClO–CHcy enabled sensitive detection of exogenous and endogenous ATP/ClO– in the lysosomes of living cells. Furthermore, it was successfully applied to visualize excess ATP and ClO– in a dextran sulfate sodium (DSS)-induced IBD mouse model. Notably, the feces of IBD mice exhibited a 1.8-fold increase in fluorescence intensity. This study offers a design strategy to develop dual-locked hemicyanine probes for diagnosis of inflammatory diseases.