Étude des effets d'impulsions électriques ultra-courtes sur des cellules vivantes : mise au point de nouveaux outils, développement théorique et premières applications in vivo

Electropermeabilization is a safe and routinely used method to transfer genes or drugs in cells or tissues. Recent studies on intra-cellular effects of nanosecond pulsed electric fields opened new ways for cell manipulation. But before thinking to clinical applications, the development of new tools is necessary. In this context, we developed new exposition devices to ultra-short pulses and we showed potential therapeutic applications, especially for cancer treatment. A new concept based on insulated electrodes was proposed to avoid any electrochemical contamination or burn of cells or tissues. The implementation of such method for in vitro and in vivo experiments permitted to increase the efficiency of luciferase production after conventionnal electrogenetransfer. Finally, the combination of bleomycin with nanosecond pulses gave complete tumor regressions. A biochip for the real-time observation of exposed cells under a microscope was also realized and included as the end element of the pulse transmission line. All the results presented in this thesis showed that it is possible to consider the use of such ultra-short pulsed electric fields as a new therapeutic tool for cancer treatment and gene therapy.