【Animal Modeling】-How to use targeted near-infrared fluorescent dyes in liver cancer models?

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

  Method: Nude mice were subcutaneously inoculated with luciferase-labeled human liver cancer cells HepG2 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. Where hematoxylin-eosin (H&Estaining) confirmed tumor occurrence, immunohistochemistry (IHC) detected the expression of CEA, AFP, HIF1α and OATP3A1 in liver cancer tumor tissue; NIRF in liver cancer cells used mitochondrial tracers (MitoTracker) and LysoTracker (LysoTracker) to identify pigments; test IR-783's ability to distinguish liver cancer cells cultured in a mixture of normal liver cells.

  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.