title: A novel plasmid and SonoVue formulation plus ultrasound sonication for effective gene delivery in nude mice.
abstract: OBJECTIVE
  This study aimed to identify the effectiveness of gene therapy mediated by ultrasound-targeted SonoVue using the herpes simplex virus-thymidine kinase (TSV-TK) driven by the kinase insert domain receptor (KDR) promoter (KDR-TK) for the treatment of ovarian carcinomas in nude mice. The optimized conditions for gene transfection were also explored.
  
  
  METHODS
  In this study, we developed a novel technique to deliver a plasmid vector-carried gene into tumor xenografts in sixty nude mice. We first mixed plasmid DNA with SonoVue to form microbubbles and then treated the mice with ultrasound sonication to enhance plasmid gene transfection and expression in tumor xenografts.
  
  
  RESULTS
  The data showed that injection of pBluescript-KDR-TK cDNA mixed with SonoVue into nude mice plus ultrasound sonication significantly (Group E) increased the transfection efficiency and expression of KDR-TK mRNA in tumor xenografts. The growth of tumor xenografts in nude mice was significantly suppressed in Group E compared to the other four control groups (Groups A, B, C, and D, namely, treatment with phosphate-buffered saline (PBS), KDR-TK+PBS, KDR-TK+SonoVue, KDR-TK+PBS+ultrasound sonication, respectively). TUNEL staining showed that SonoVue plus ultrasound sonication significantly induced apoptosis and reduced microvessel density (MVD).
  
  
  CONCLUSIONS
  This study revealed that the formulation of plasmid with SonoVue plus ultrasound could provide efficient gene delivery into tumor xenografts. Increased gene expression was observed in vivo, which effectively reduced the tumor growth and MVD of tumor xenografts and induced apoptosis in tumor cells. Future clinical trials are necessary to further analyze the relevance of this technique.
authors.affiliation: Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xin-Lu
authors.initials: XL
authors.lastname: Wang
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Zhao
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Jia
authors.forename: Luo
authors.initials: L
authors.lastname: Jiang
authors.forename: Tei-Mei
authors.initials: TM
authors.lastname: Shi
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D010743:Phospholipids / Q000235:genetics*; D010957:Plasmids / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics*; D013010:Sonication; D013459:Sulfur Hexafluoride; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010743:Phospholipids; C420843:contrast agent BR1; D013937:Thymidine Kinase; D040301:Vascular Endothelial Growth Factor Receptor-2; D013459:Sulfur Hexafluoride
keywords: Gene therapy; Microbubbles; Ovarian neoplasms; Transfection; Ultrasound