Imaging Fibrosis Progression in NASH with an Allysine-Reactive AIE Probe

Nonalcoholic steatohepatitis (NASH) is prevalent in the global population, where up to one-third of patients would further progress to developing fibrosis, cirrhosis, and hepatocellular carcinoma, thereby increasing liver-related mortality. Since fibrosis worsens the prognosis in NASH, developing a method to monitor fibrosis activity in NASH is demanded. Considering that lysyl oxidase (LOX), an enzyme that promotes crosslinking of extracellular matrix, plays an important role in fibrosis, collagen with an aldehyde group as LOX-catalyzed product can be utilized as a molecular imaging target for fibrosis detection. LOX can oxidize lysine with an amine group on collagen to allysine with an aldehyde group. Here, we developed an activatable imaging probe TPAH with an aggregation-induced emission (AIE) property. Its fluorescence can be turned on due to restricted intramolecular motion after reaction with collagen in the active fibrogenesis site with enhanced LOX activity. In vivo studies demonstrated that NASH mice showed stronger fluorescence signal in the liver than healthy mice after intravenous administration of TPAH. However, the enhanced fluorescence signal in NASH mice was markedly weakened after treatment with a LOX inhibitor, validating the LOX specifity of the allysine-reactive AIE probe. Therefore, TPAH is promising to monitor fibrosis progression at an early stage in NASH.