Abstract 200: Application of nanobubbles for HSV-tk/GCV cytotoxic gene therapy using ultrasound.
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 56
M. Suzuki1, F. Shinohara2, A. Aoi3, Y. Sato3, Y. Watanabe1, S. Mori2, G. Vassaux4, T. Kodama1
1Tohoku University Biomedical Engineering Research, Sendai, Japan
2Tohoku University Hospital, Sendai, Japan
3Tohoku University Graduate School of Dentistry, Sendai, Japan
4Cancer Research UK Clinical Centre, John Vane Science Centre, London, United Kingdom
Herpes simplex virus thymidine kinase (HSV-tk) gene has been demonstrated by several investigators to confirm cytotoxic sensitivity by ganciclovir (GCV) in various tumor cells.
Destruction of nanobubbles (NB) mediated ultrasound (US) has been proposed as an innovative method for noninvasive delivering of genes to the tissues of interest.
In this report, we evaluated the effectiveness of HSV-tk/GCV cytotoxic gene therapy in cancer cells using NB combined with US in vitro.
We transduced HSV-tk gene into five cell lines (A549, MCF7, EMT6, colon 26 and 293T cells) using albmin or lipid nanobubbles (10% v/v) under the optimized US conditions (frequency:945 kHz, duty ratio:50%, pressure: 0.96 MPa).
The mRNA of HSV-tk expression was detected by RT-PCR at 24 h after gene transfer. The anti-cancer effects of GCV treatment were evaluated using MTT assay at 6 days after gene transfer. Significant cytotoxity was obtained in only treated cells which expressed the mRNA of HSV-tk, compared to untreated cells.
These results suggest that GCV phosphorylated with HSV-tk would induce specific cytotoxity to transfected cancer cells.
We believe that gene delivery using nanobubbles could be useful for cancer specific gene therapy.
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