| Malignant tumors have become one of the most serious public health problems all over the world While liver cancer has always been one of the most prevalent and fatal malignant tumors.The traditional methods of hepatocellular carcinoma diagnosis and screening are imaging examination and serum marker detection.However,because of the genome instability and high heterogeneity of hepatocellular carcinoma,it lacks early diagnosis methods for hepatocellular carcinoma which makes most patients have been diagnosed at an advanced stage.The early treatment of hepatocellular carcinoma mostly adopts surgical treatment,and the comprehensive treatment such as radiotherapy,chemotherapy and immunotherapy for advanced tumors.Although the short-term curative effect has been improved,the long-term curative effect is still not ideal.Therefore,the search for a more effective new strategy for the treatment of liver cancer has become the current research focus.Due to its high expression in hepatocellular carcinoma cells,Glypican-3(GPC3)is highly specific for the diagnosis and treatment of hepatocellular carcinoma.A humanized antibody GC33 which targets the c-terminal of GPC3 has been reported to enter the phase Ⅱ clinical stage.However,GC33 has not shown clinical efficacy,indicating that monoclonal antibody may have limitations in the treatment of hepatocellular carcinoma.In terms of early diagnosis of hepatocellular carcinoma,indocyanine green(ICG)is characterized by small toxic and side effects,short half-life,low signal-to-noise ratio,non-absorption by extrahepatic tissues,and potential of photodynamic killing,etc.In recent years,the near-infrared imaging ability of ICG has been widely used in the diagnosis of hepatocellular carcinoma,and it has also been reported to attempt to use its photothermal characteristics to kill hepatocellular carcinoma cells.However,ICG also has the disadvantages of low specificity and poor penetration which limits its use.In this study,Balb/C mice were immunized with the purified c-terminal part of GPC3 protein expressed by the baculovirus system.Six strains of monoclonal antibodies which are specific to GPC3 target of hepatocellular carcinoma were screened and verified.1B11 was selected for its strongest binding ability to antigen GPC3-C among the six monoclonal antibodies,and it possibly binds the same epitope of GPC3 as GC33.The in vitro binding ability of IB 11 to Huh7,HepG2 and other hepatocellular carcinoma cells and the high specificity of GPC3 target were identified and verified.1B 11 was coupled with ICG-NHS ester to construct 1B11-ICG,which was purified by ZebarTM desalination centrifuge column,and showed the same specific recognition ability for hepatocellular carcinoma as 1B11 in vitro experiments.In the subcutaneous tumor-bearing mice,1B11-ICG showed the ability to exert the near infrared fluorescence imaging and photothermal treatment ability of ICG by targeting tumor sites through the mediating of 1B11.What’s more,1B 11-ICG showed biosafety in mice after photothermal treatment.The experimental results indicated that our 1B11-ICG combined the advantages of 1B 11 and ICG,so that it can improve the tumor specificity of imaging in hepatocellular carcinoma diagnosis,and at the same time,it can also play an efficient photothermal treatment effect.The feasibility of its application in detection and diagnosis of liver cancer was preliminarily explored,providing some new ideas for solving the difficulties in early diagnosis and immunotherapy of hepatocellular carcinoma. |
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