A galactose-mediated targeting nanoprobe for intracellular hydroxyl radical imaging to predict drug-induced liver injury.

Drug-induced liver injury (DILI) is a serious concern in modern medicine due to its unpredictability. Currently, biochemical serum markers are being used in DILI detection. However, these biomarker-based methods lack sensitivity and specificity. A high intracellular level of hydroxyl radicals (˙OH) has been regarded as an early indicator of DILI. Therefore, we proposed an ˙OH-responsive and hepatocyte-targeted nanoprobe conjugation of carboxyfluorescein-labeled DNA and pegylated galactose on the surface of gold nanoparticles. The nanoprobe could bind to a hepatocyte-specific asialoglycoprotein receptor through galactose, and it could be internalized into liver cells. In the presence of high levels of ˙OH in DILI, the DNA could be cleaved to release carboxyfluorescein, leading to remarkable fluorescence enhancement for ˙OH detection. Confocal fluorescence imaging demonstrated that the nanoprobe could be successfully applied in monitoring high ˙OH levels resulting from acetaminophen or triptolide-induced liver injury, which may provide a simple but powerful protocol for the prediction of DILI.