An activatable “AIE + ESIPT” fluorescent probe for dual-imaging of lipid droplets and hydrogen peroxide in drug-induced liver injury model

Abstract

Background

Drug-induced liver injury (DILI) is one of the most common liver diseases. The crucial role of lipid droplets (LDs) and hydrogen peroxide (H₂O₂), two important biomarkers in the pathophysiology of DILI, has spurred considerable efforts to accurately visualize H₂O₂ and LDs for elucidating their functions in the progression of DILI. However, construction of a single fluorescent probe that is able to simultaneously image H₂O₂ and LDs dynamics remains to be a challenging task. Therefore, it is of great demand to develop a novel fluorescent probe for tracking the LDs status and H₂O₂ fluctuation in drug-induced liver injury.

Results

We developed an “AIE + ESIPT” fluorescent probe TPEHBT for dual-imaging of LDs and H₂O₂ during DILI process. TPEHBT displayed greatly enhanced fluorescent response to H₂O₂ by generating an excited state intramolecular proton transfer (ESIPT) fluorophore TPEHBT-OH with aggregation induced emission (AIE) properties. TPEHBT exhibits high selectivity, sensitivity (LOD = 4.73 nM) and large Stokes shift (320 nm) to H₂O₂. Interestingly, TPEHBT can light up LDs with high specificity. The probe was favorably applied in the detection of endogenous and exogenous H₂O₂ in living cells, and notably in the simultaneous real-time visualization of H₂O₂ generation and LDs accumulation during DILI process. Moreover, TPEHBT was able to image H₂O₂ generation in zebrafish animal model with APAP-induced liver injury.

Significance

For the first time, probe TPEHBT was applied in the dual-imaging of H₂O₂ fluctuation and LDs status in APAP-induced liver injury model in vitro and in vivo. The present findings strongly suggest that TPEHBT is a promising tool for monitoring H₂O₂ and LDs dynamics in DILI progression.