Ultrasound-Enhanced Chemotherapy and Gene Delivery for Glioma Cells

• Published in: Technology in cancer research & treatment 2007-10, Vol.6 (5), p.433-442
• Main Authors: Zarnitsyn, Vladimir G., Kamaev, Pavel P., Prausnitz, Mark R.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Biological and medical sciences; Bleomycin - administration & dosage; Carmustine - administration & dosage; Cell Survival; Combined Modality Therapy; DNA - administration & dosage; Dose-Response Relationship, Drug; Gene Transfer Techniques; Genetic Therapy - methods; Gliosarcoma - therapy; Green Fluorescent Proteins - administration & dosage; Green Fluorescent Proteins - genetics; Medical sciences; Neurology; Rats; Transfection; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses; Ultrasonic Therapy
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/153303460700600509

Treatment of brain cancer is limited in part by inefficient intracellular delivery of drugs and DNA for chemotherapy and gene therapy, respectively. This study tested the hypothesis that ultrasound may be used to enhance intracellular delivery and efficacy of chemotherapeutics and genes in glioma cells in vitro. First, suitable ultrasound conditions were identified by measuring intracellular uptake of calcein and viability of GS 9L rat gliosarcoma cells after a range of different ultrasound exposures. We selected sonication at 10 J/cm2, which achieved intracellular delivery of ν106 molecules/cell. Next, glial cells were sonicated with varying concentrations of model chemotherapeutics: BCNU and bleomycin. For both drugs, cytotoxicity was increased in a synergistic manner when accompanied by ultrasound exposure. Finally, expression of a plasmid DNA encoding a GFP reporter was increased up to 30-fold when exposed to ultrasound. Altogether, these findings suggest that ultrasound may be useful to increase the efficacy of chemotherapy and gene therapy of glioma cells.