The Experimental Studies To Strengthen The Damaging Effects Of RFA On Rabbit VX2 Liver Cancer Model By GNPs-VEGFsiRNA Targeting By TyrRGD

Objective and significance:Hepatocellular carcinoma(HCC)is one of the most common malignant tumors,and is the third leading cause of cancer mortality worldwide.Radiofrequency ablation(RFA)as an important means of treating liver cancer in clinic,has several advantages,such as definitive therapeutic effect,minimal invasiveness,safety,repeatability,and shorter hospitalization.But,the one-time finite damage volume,resulting in not all lesions damage that large hepatocellular carcinoma after RFA treatment and the presence of residual cancer,is the main defect of RFA.How to increase the one-time damage volume of RFA and reduce the residual cancer after RFA is the key to improve the efficacy of RFA.Therefore,this paper bases on TryRGD-GNPs-VEGFsi RNA which has been compounded by other member of research group,planning to combine the basic principle and in vivo study,to investigate the impact on the damaging effects of Radiofrequency ablation(RFA)on rabbit VX2 liver cancer model by GNPs-VEGFsi RNA targeting by TryRGD.In order to provides new ideas and methods to reduce the rate of residual tumor after RFA,to improve the curative effect of RFA.Methods:63 New Zealand rabbit were slected to establish the rabbit models of liver cancer by opening the abdominal cavity directly and planting VX2 tumor tissue.After3 weeks,rabbit models were randomly divided into 3 groups,namely group A:injection of Tyr RGD-GNPs-VEGFsi RNA compounds(N=22)Group B:injection of GNPs(N=13)and the group C:injection of normal saline(N=28).48 hours later,slecting 3 rabbits from group A,3 rabbits from group B,use transmission electron microscopy to detect the gather of complex in the tumor sample.Then,select 10 rabbit from each group to have RFA therapy,2 days later,cut tumor specimen,using hematoxylin and eosin staining to confirm histologic analysis;ruler to measure the damage volume;TUNNEL kit to detect the residual cancer cell apoptosis.The rest of the VX2 rabbit divided into three groups,,namely the RFA combined TyrRGD-GNPs-VEGFsi RNA complex group(N=9),RFA combined physiological saline group(N=9)and physiological saline group(N=9),all of the rabbits died a natural death,record the time to live.Results:(1)Established VX2 rabbit liver tumor models successfully.(2)The distribution of Tyr RGD-GNPs-VEGFsi RNA compound in the tumor was superior to that of the naked GNPs(P<0.01).(3)The damage volume of TyrRGD-GNPs-VEGFsi RNA group(5.71±2.12 cm~3)was significantly greater than that of GNPs group(1.78±0.46 cm~3)and normal saline group(1.49±0.44 cm~3)(P<0.01),but there was no significant statistical difference between GNPs group and normal saline group(P>0.05).(4)TUNEL method showed that Tyr RGD-GNPs-VEGFsi RNA complex group had much more apoptosis of cancer cells than that in the other tow groups.(5)Existent time in RFA combined TyrRGD-GNPs-VEGFsi RNA complex group was significantly longer than that in RFA combined physiological saline group and physiological saline group(P<0.01).Conclusion:TyrRGD-GNPs-VEGFsiRNAcomplexes can gather in the liver tumor preferably and have better target tropism.In addition,they can enhance the damaging effects of RFA to tumor,and promote the residual cancer cells apoptosis.