Experimental Study Of Doxorubicin-loaded Polyethylene Glycol-coated Hollow Gold Nanospheres Combined With Irreversible Electroporation(IRE)in The Treatment Of Rat Hepatocellular Carcinoma

Objective:To study the feasibility and stability of SD rat McA-RH7777 hepatocellular carcinoma model.To evaluate the safety and feasibility of rat hepatic artery catheterization and present a modified method for retrograde administration of the gastroduodenal artery.To evaluate the possibility that Dox@PEG-HAuNS can pass through the IRE induced perforations on cell membrane,kill cancer cells upon intracellular release of DOX and improved therapeutic efficacy with decreased tumor recurrence rate can be expected.Materials and Methods:The anesthesiaed rats were injected McA-RH7777 cells.The long diameter of the tumor is measured.The tumor tissues were detected by HE staining and VEGF.The rats were treated with modified gastroduodenal artery catheterization and the operation time,intraoperative and postoperative condition were recorded.The anesthesiaed rats were injected McA-RH7777 cells.The long diameter of the tumor is measured.The tumor tissues were detected by HE staining and VEGF.The rats were treated with modified gastroduodenal artery catheterization and the operation time,intraoperative and postoperative condition were recorded.The 25 rats which were successfully built the tumor were randomly divided into blank control group,lipiodol group,lipiodol and doxorubicin mixed suspension group,Dox@PEG-HAuNS combined with lipiodol group,Dox@PEG-HAuNS combined with lipiodol and Irreversible Electroporation group.Each therapy treated the rats of groups on the 9th day after trumor biult operation.The rats of each group were examined by MR and CT after 7 days,14 days and 21 days of laparotomy.ALP,ALT,AST,CREA,UREA of vein blood were detected and the rats were sacrificed after 14 days of laparotomy.The tumor tissues were detected by HE staining,TUNEL,CD31,KI67 and VEGF at the same time.Results:The rate of successfully formed tumor is 90%in the experimental study.The tumors are growing fast in the first two weeks and regressing in the third week after tumor building.The rate of successful hepatic artery catheterization is 100%.The operation time is 24.7±9.7min and the condition is normal after the operation.After 14 days of laparotomy,the long diameters of tumor are 23.3±4.4mm(blank control group),17.2±1.7mm(lipiodol group),15.6±1.9mm(lipiodol and doxorubicin mixed suspension group),11.2±1.9mm(Dox@PEG-HAuNS combined with lipiodol group),10.8±1.5mm(Dox@PEG-HAuNS combined with lipiodol and Irreversible Electroporation group).There are significant differences in long diameter of each group(P=0.00).There are no significant differences in the results of vein blood examining in each group(P>0.05).The results of pathological and immunohistochemical exame show that the inhibiting effect of each therapy group is obvious compared to the blank control group and the effect of Dox@PEG-HAuNS combined with lipiodol and Irreversible Electroporation group is the most significant.Conclusions:The model of SD rat McA-RH7777 Hepatocellular Carcinoma is viable,stable and safe.The modified method for retrograde administration through the rat's gastroduodenal artery is an efficient,feasible and safe method of administration.Dox@PEG-HAuNS can pass through the IRE induced perforations on cell membrane,thus kill cancer cells upon intracellular release of DOX.Therefore improved therapeutic efficacy with decreased tumor recurrence rate can be expected.