Objective: To explore the application of the near-infrared fluorescent dye IR-783 of heptamethrin in imaging research of liver cancer models, and analyze the molecular mechanism of the dye targeting tumor cells.
Method: HepG2 liver cancer cells labeled with luciferase were subcutaneously inoculated into nude mice to test the correlation between bioluminescence (BIL) signal and NIRF signal at the site of tumor occurrence. Establish a patient driven xenograft (PDX) model of human liver cancer in nude mice using renal subcapsular transplantation, and observe the ability of IR-783 to recognize tumor boundaries; Hematoxylin eosin staining (H&E staining) confirms the location of tumor occurrence, and immunohistochemistry (IHC) detects CEA, AFP, and HIF1 in liver cancer tumor tissue α And the expression of OATP3A1; Confirm the binding site of NIRF dye in liver cancer cells using Mito Tracker and Lyso Tracker; Test the discriminative ability of IR-783 on liver cancer cells mixed with normal liver cells.
Result: There is a good correlation between BIL and NIRF intensity in subcutaneous transplantation of human liver cancer in nude mice; NIRF dye IR-783 can clearly recognize the edges of liver cancer tumors after renal capsule transplantation; IHC staining shows CEA, AFP, and HIF1 in tumor tissue α Both OATP3A1 and OATP3A1 are highly expressed; IR-783 mainly binds to the mitochondria and lysosomes of tumor cells; Human liver cancer cells HepG2 labeled with GFP can be specifically recognized by IR-783.
Conclusion: IR-783 is a novel near-infrared fluorescent dye with tumor targeting and imaging characteristics, and its targeting potential may be related to HIF1 in liver cancer tissue α Related to high expression of OATP3A1.