title: Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma.
abstract: Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Novel selenium-substituted hydroxyapatite nanoparticles (SeHAN) were designed to serve as anticancer agent. The authors examined the nanoparticles by physicochemical techniques. The in vivo efficacy and toxicity of these nanoparticles were also investigated on a nude mice model of human hepatocellular carcinoma. The results showed that the selenite ions can be incorporated into the hydroxyapatite lattice facilely. They exhibited bundles of needles shape with a size of 160-200 nm. In the in vivo study, they showed better survival advantage. The overall survival rate of nude mice in the control, pure hydroxyapatite and SeHAN group were 50.00%, 76.92%, and 100.00% respectively. Blood biochemical studies showed that SeHAN group had significantly lower toxicities on the liver and kidney functions. Histopathological studies confirmed that massive tumor necrosis and calcium deposition were evident after SeHAN treatment. Moreover, immunohistochemistry and Western blot assay showed significantly reduced expression of the Ki-67, VEGF and MMP-9 protein in the SeHAN group. Taken together, these results suggest that the selenium-substituted hydroxyapatite nanoparticles could be a new type of promising anticancer agent to provide both survival advantage and lower toxicity.
authors.affiliation: Medical Science College of China Three Gorges University, Yichang, China. Electronic address: juddy0921@163.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Yanhua
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012643:Selenium / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014961:X-Ray Diffraction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D017886:Durapatite; D020780:Matrix Metalloproteinase 9; D012643:Selenium
keywords: Hepatocellular carcinoma; In vivo test; Nanoparticle; Selenium-substituted hydroxyapatite