Visualization of hepatic fibrosis and assessment of therapeutic effect by an asymmetric BODIPY fluorescent probe capable of dually detecting lipid droplets and nitric oxide.

Hepatic fibrosis represents a critical stage in the progression of chronic liver disease. Nitric oxide (NO) and lipid droplets (LDs), as important biomarkers, are closely associated with the pathogenesis of hepatic fibrosis. Effective tracking of changes in NO and LDs is beneficial for detecting hepatic fibrosis and assessing the therapeutic effect of anti-hepatic fibrosis drugs. However, there is currently a lack of small-molecular fluorescent probes that are able to simultaneously target LDs and sense NO, and elucidate their relationship with hepatic fibrosis. Herein, we developed a LDs-targeting and NO-sensitive fluorescent probe (BDP-NO) based on an asymmetric BODIPY skeleton for the diagnosis of hepatic fibrosis in vitro and in vivo. Upon the addition of NO, BDP-NO demonstrated a fluorescence "turn-on" effect with a significant Stokes shift of 84 nm, and exhibited strong sensitivity (LOD = 0.50 μM), selectivity and a quick response time (within 1 min) for NO. Notably, BDP-NO was successfully used to target LDs and simultaneously monitor exogenous and endogenous NO in hepatic fibrosis models. Furthermore, BDP-NO could differentiate mild fibrotic stages from severe ones, and allowed for monitoring of therapeutic effect by enhanced fluorescence imaging. Therefore, BDP-NO exhibited significant potentials in diagnosing NO and LDs-mediated hepatic fibrosis and evaluating its treatment.