Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo,which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.Methods:Humanized anli-VECFR-2 ScFv-As_2O_3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology.In this combined in vitro and in vivo study,the inhibitory effects of anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles conjugate on tumor growth,invasion,and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay,Tanswell assay,Hochest33258 staining,and DNA ladder analysis.The anticancer activity and distribution of anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles was then verified in a mouse model of Bel7402xenografts.Results:Anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yh-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells.And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis.Transwell assay found that the drug also inhibited the metastasis ability of tumor cells.Furthermore,anti-VEGFR-2 ScFv-As^-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration(92.9%),followed by As_2O_3-stealth nanoparticles,anti-VEGFR-2 ScFv,and As203(61.4%,58.8%,20.5%,P<0.05).The concentration of As_2O_3 in anti-VEGFR-2 ScFv-As_2O_3-steallh nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.
Xiang-Bao YinLin-Quan WuHua-Qun FuMing-Wen HuangKai WangFan ZhouXin YuKai-Yang Wang
