A Pair of Fluorescent Probes Enabling Precise Diagnosis of Liver Cancer by Complementary Imaging

Hepatocellular carcinoma (HCC) is by far the predominant malignant liver cancer, with both high morbidity and mortality. Early diagnosis and surgical resections are imperative for improving the survival of HCC patients. However, limited by clinical diagnosis methods, it is difficult to accurately distinguish tumor tissue and its boundaries in the early stages of cancer. Herein, we report two fluorescent probes, cLG and hLR, for the detection of cancer and healthy cells, respectively, enabling the precise diagnosis of liver cancer by providing complementary imaging. These two fluorescent probes could selectively stain the target cells in the liver tissue imaging, which is confirmed by H&E and antibody staining. Moreover, for the first time, the cancerous area and healthy area are clearly identified by the cocktail of these two probes, suggesting its potential to be used in fluorescence-guided surgery. Finally, we identify transporter SLC27A2 as the gating target of cLG through a systematic transporter screen using a CRISPR activation library. SMPD1 was identified as the target of hLR through a thermal proteome profiling. Therefore, the development of these two highly specific probes offers complementary imaging and provides a unique diagnostic tool for cancer disease, even for fluorescence-guided surgery.