A superoxide anion activatable 7-Azaindole derived photoacoustic probe for high-contrast imaging of drug-induced liver injury

The accurate diagnosis of Drug-induced liver injury (DILI) plays essential role for the effective treatment and avoiding the worsening of liver injury. Considering superoxide anion (O-2(center dot-)) is closely associated with the progression of DILI, molecular probes that achieve high-contrast photoacoustic (PA) imaging of O-2(center dot-) in deeper tissues with high spatial resolution are valuable tools for the accurate diagnosis of DILI. However, the existing PA probes for O-2(center dot-) display the relatively short absorption wavelength and small bathochromic shift, limiting their PA activation folds. Here we construct a new O-2(center dot-) activatable 7-Azaindole derived probe (AIH-OTF) for PA imaging of DILI in vivo. A novel 7-Azaindole modified hemicyanine dye (AIH-OH) is incorporated as the PA reporter of AIHOTF due to its long absorption wavelength, large molar extinction cofficient and low fluorescence quantum yield. It is demonstrated that AIH-OTF exhibits the highly sensitive and selective PA response to O-2(center dot-) with a large bathochromic shift (203 nm) and high activation fold (9.7 times). Cellular studies indicate that AIH-OTF can realize high-contrast PA imaging of the dynamic changes of endogenous O-2(center dot-) in living cells. AIH-OTF is successfully applied to detect the occurrence of drug-induced liver injury and assess the therapeutic efficacy through its PA response to O-2(center dot-). We expect that AIH-OTF may serve as a useful imaging tool for the diagnosis and pathogenesis research of DILI.