【Animal Modeling】-Targeted near-infrared fluorescent dyes in liver cancer models

  Objective: To explore the application of near-infrared fluorescence (IRRF) dye IR-783 in imaging studies of liver cancer models, and to analyze the molecular mechanism of the dye targeting tumor cells.

  Method: Inoculate luciferase-labeled human liver cancer cells HepG2 subcutaneously into nude mice to test the correlation between tumor site bioluminescence (BIL) and NIRF signal. A xenograft (PDX) model for human liver cancer patients was established by subcapsular transplantation, and the ability of IR-783 to recognize tumor boundaries was observed. Hematoxylin-eosin staining (H and staining) confirmed the development of the tumor. Location, immunohistochemistry (Immunohistochemistry), IHC) to detect the expression of CEA, AFP, HIF1α and OATP3A1 in hepatocellular carcinoma tumor tissue; MitoTracker and lysosome tracer (MitoTracker) and lysosome tracer The tracer (LysoTracker) was used; the binding site of IR -783; the ability of IR-783 to distinguish hepatocellular carcinoma cells cultured in a mixture of normal hepatocytes was tested.

  Result: The BIL of human liver cancer transplanted subcutaneously into nude mice is closely related to the intensity of NIRF. IRF dye IR-783 can clearly identify the tumor end of renal capsule transplanted liver cancer. IHC staining showed CEA, AFP, and HIF1α. , And the tumor tissue OATP3A1HIF1α is highly expressed. IR-783 mainly binds to the mitochondria and lysosomes of tumor cells. GFP-labeled human liver cancer cells HepG2 are specifically recognized by IR-783.

  Conclusion: IR-783 is a new type of near-infrared fluorescent dye with tumor targeting and imaging properties. Its targeting effect may be related to the high expression of HIF1α and OATP3A1 in liver cancer tissues.