Cascaded fingerprint recognition for non-alcoholic steatohepatitis imaging

Abstract

Non-alcoholic steatohepatitis (NASH) represents a critical stage within metabolic dysfunction-associated fatty liver disease (MAFLD), spanning from mere steatosis to cirrhosis. Timely and accurate diagnosis is of paramount importance for disease monitoring and effective therapeutic intervention. However, the current gold standard for diagnosis in clinical settings, biopsy, is hindered by its invasiveness and sample variability. The lack of reliable noninvasive diagnostic methods has created an urgent need for the development of innovative imaging techniques, particularly those utilizing activatable fluorescent probes capable of recognizing multiple NASH-specific fingerprints. Recognizing that inflammation and lipid droplet accumulation are fingerprints of NASH, we have engineered a molecular probe, TBPB, which is specifically designed to trigger a fluorescence turn-on response only when these two most cardinal features coexist. This unique cascaded fingerprint recognition strategy of TBPB holds immense potential for enhancing the specificity and sensitivity of NASH diagnosis. Through a series of in vitro studies, we have demonstrated that TBPB exhibits a robust response in NASH-mimicking scenarios and could selectively activate its fluorescence signal in the presence of both inflammation and lipid droplet accumulation. Furthermore, our in vivo studies have provided compelling evidence for the translational potential of TBPB, showcasing its ability to accurately diagnose NASH in animal models.