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

Abstract

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 <i>in situ</i> targeting ability are the key to improving the imaging effect of liver injury. Herein, we rationally designed a leucine aminopeptidase (LAP) activated fluorogenic probe <b>hCy-CA-LAP</b>, which greatly improved the hepatocyte-targeting capability by introducing a cholic acid group. The probe <b>hCy-CA-LAP</b> is converted into a high-emission <b>hCy-CA</b> 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 <i>in situ</i> accumulation in the liver, thereby achieving precise imaging and evaluation of two different types of drug-induced hepatotoxicity <i>in vivo</i>. Therefore, the probe <b>hCy-CA-LAP</b> may be a potential tool for exploring the roles of LAP and evaluating the degree of DILI.