A pH‐Responsive Glycyrrhetinic‐Acid‐Modified Small‐Molecule Conjugate for NIR Imaging of Hepatocellular Carcinoma (HCC)

We report a glycyrrhetinic‐acid (GA)‐decorated small‐molecule conjugate for pH‐triggered near‐infrared (NIR) fluorescence imaging of hepatocellular carcinoma (HCC). Our in vitro studies demonstrated that the conjugate, referred to as NIR‐GA, was efficiently taken up by liver cancer cell lines such as HepG2 and Huh7 through an endocytic pathway mediated by GA receptors. As suggested by co‐localization studies, NIR‐GA mainly localized in the lysosome, where the acidic pH results in the activation of the fluorescent dye through H+‐triggered spirolactam ring opening to give strong fluorescence in the NIR region. NIR fluorescence imaging of liver cancer cells: We report NIR‐GA, a glycyrrhetinic‐acid (GA)‐decorated small‐molecule conjugate for pH‐triggered NIR imaging of hepatocellular carcinoma (HCC). It exhibits high pH selectivity, and photostability. In vitro studies found NIR‐GA was easily taken up by HCC cells through an endocytic pathway mediated by GA receptors without cell viability being compromised.