A novel plasmid and SonoVue formulation plus ultrasound sonication for effective gene delivery in nude mice

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.

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.

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).

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.