title: Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo studies.
abstract: OBJECTIVE
  To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-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 anti-VEGFR-2 ScFv-As2O3-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-As2O3-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-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402 xenografts.
  
  
  RESULTS
  Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-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-As2O3-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2 ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively.
  
  
  CONCLUSIONS
  Anti-VEGFR-2 ScFv-As2O3-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.
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China. Electronic address: yxb115@sina.com.
authors: Xiang-Bao
authors: XB
authors: Yin
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Lin-Quan
authors: LQ
authors: Wu
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Hua-Qun
authors: HQ
authors: Fu
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Ming-Wen
authors: MW
authors: Huang
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Kai
authors: K
authors: Wang
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Fan
authors: F
authors: Zhou
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Xin
authors: X
authors: Yu
authors: Department of Hepatobiliary Surgery, 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
authors: Kai-Yang
authors: KY
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D008113:Liver Neoplasms; D008114:Liver Neoplasms, Experimental; D051379:Mice; D055806:Microvessels / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000473:pathology; D010087:Oxides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D057127:Single-Chain Antibodies; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077237:Arsenic Trioxide
keywords: Anti-VEGFR-2 single-chain antibody conjugate; As(2)O(3) stealth nanoparticles; Hepatocellular carcinoma