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.
Subject(s)
Animals , Humans , Mice , Antineoplastic Agents , Chemistry , Pharmacokinetics , Pharmacology , Apoptosis , Arsenic Trioxide , Arsenicals , Chemistry , Pharmacokinetics , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Drug Delivery Systems , Liver Neoplasms , Liver Neoplasms, Experimental , Microvessels , Nanoparticles , Chemistry , Metabolism , Neovascularization, Pathologic , Pathology , Oxides , Chemistry , Pharmacokinetics , Pharmacology , Single-Chain Antibodies , Chemistry , Metabolism , Vascular Endothelial Growth Factor Receptor-2 , MetabolismABSTRACT
Objective To prepare a new type of chitosans nanoparticles(PEG/CS-EPI NPs),which contains epirubicin and modified by PEG.Furthermore,to investigate the anticancer activity of the NPs in vitro and in vivo.Methods The ionic gelation technique was employed to prepare the PEG/CS-EPI NPs and CS-EPI NPs.The particle size and shape were illustrated respectively by laser scattering and transmission electron microscopy.The proliferation of nasopharyngeal carcinoma cells was detected by MTT assay;The mouse model of implantation murine sarcoma cells(S-180) was applied to evaluate the anticancer effectiveness of PEG/CS-EPI NPs and CS-EPI NPs in vivo.Results The PEG modified CS NPs were discrete and uniform spheres with average diameter of 322.1 nm.The rate of drug loading and encapsulation is 13% and 74% respectively.The results of the anticancer tests showed a sustained cytotoxicity of loading drug NPs on nasopharyngeal carcinoma cells in vitro and the stealth nanoparticles was more powerful than ordinary nanoparticles on the inhibitory potency in vivo.Conclusion Stealth chitosan nanoparticles as compared with ordinary chitosan nanoparticles seems to be a potential candidate of chemotherapy drug carriers.