Enzyme-activated near-infrared fluorogenic probe with high-efficiency intrahepatic targeting ability for visualization of drug-induced liver injury.

Hepatotoxicity is a serious problem faced by thousands of clinical drugs, and drug-induced liver injury (DILI) caused by chronic administration or overdose has become a major biosafety issue. However, the near-infrared (NIR) fluorescent probes currently used for liver injury detection still suffer from poor liver targeting ability and low sensitivity. Enzyme-activated fluorogenic probes with powerful in situ targeting ability are the key to improving the imaging effect of liver injury. Herein, we rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe hCy-CA-LAP, which greatly improved the hepatocyte-targeting capability by introducing a cholic acid group. The probe hCy-CA-LAP is converted into a high-emission hCy-CA fluorophore in the presence of LAP, showing high selectivity, high sensitivity and low detection limit (0.0067 U mL-1) for LAP, and successfully realizes the sensitive detection of small fluctuations of LAP in living cells. Moreover, the probe can achieve effective in situ accumulation in the liver, thereby achieving precise imaging and evaluation of two different types of drug-induced hepatotoxicity in vivo. Therefore, the probe hCy-CA-LAP may be a potential tool for exploring the roles of LAP and evaluating the degree of DILI.