Leucine Aminopeptidase-Mediated Multifunctional Molecular Imaging Tool for Diagnosis, Drug Evaluation, and Surgical Guidance of Liver-Related Diseases

Traditional molecular imaging tools used for detectingliver diseasesown several drawbacks, such as poor optical performance and limitedapplicability. Monitoring the concentration of leucine aminopeptidase(LAP), which is closely related to liver diseases such as liver cancerand liver injury, and analyzing it in diagnosis, drug evaluation,and surgical treatment is still a challenging task. Herein, we constructan intramolecular charge-transfer mechanism-based, ultrasensitive,near-infrared fluorescent probe (LAN-lap) for dynamic monitoring ofLAP fluctuations in living systems. LAN-lap, with high specificity,stability, sensitivity, and water solubility, can achieve in vitromonitoring of LAP through both fluorescence and colorimetric methods.Moreover, LAN-lap can successfully be used for the localization imagingof endogenous LAP, confirming the upregulation of LAP expression inliver cancer and liver injury cells. In addition, LAN-lap can realizethe imaging of liver tumors in living organisms. Meanwhile, it canintuitively present the degree of drug-induced liver injury, achievingsemi-quantitative imaging evaluation of the hepatotoxicity of twodrugs. Furthermore, LAN-lap can track liver cancer tumors in micewith peritoneal metastasis and can assist in fluorescence-guided surgicalresection of liver cancer tumors. This multifunctional LAN-lap probecould play an important role in facilitating simultaneous diagnoses,imaging, and synergistic surgical navigation to achieve better point-of-caretherapeutic efficacy.