Colloquium: How In Vivo Imaging of Electroporation Processes Can Improve its Development In Clinics
Sep 19, 2017
4:10 PM - 5:00 PM
Iacocca Hall - B-023
111 Research Drive
Bethlehem PA 18015
Muriel Golzio, PhD, Institute of Pharmacology and Structural Biology, Toulouse, France.
Sponsored by the Biological Sciences and Bioengineering Departments.
Electropermeabilization/electroporation (EP) is one of the non-viral delivery methods based on the native transmembrane electric potential modulation of the cell by applying electric pulses to cells. The selective permeability of the membrane disappears when threshold values of the transmembrane potential are reached. Permeabilization can be adjusted by the different electric parameters (intensity, number of pulses and duration) (1). This physical method thus enables the delivery of chemotherapeutic drugs into tumor cells in Electrochemotherapy (ECT) (2) or nucleic acids for gene therapy purposes in Electrogene therapy (EGT) (3) in healthy or cancerous tissues. In the field of electroporation-based treatments, imaging techniques are powerful tools to observe the bio-distribution of molecules, to describe the mechanisms of their electro-delivery and to quantify their biological effects at the level of the organs or tissues as well as the level of the cell in living animal.
We have investigated by in vivo fluorescence macroscopy, the kinetic and the efficiency of electrically-mediated delivery of nucleic acids (DNA, Minicircle, shRNA and siRNA) into tumors (4). In vivo, EP results in decreased blood flow and increased permeability of blood vessel walls. We have evaluated by intravital microscopy the effects of electric pulses used for ECT on blood vessels and on endothelial cells (5, unpublished data). Finally, we have used a transgenic mouse that expresses the luciferase reporter gene under a thermal stress inducible promoter to evaluate “thermal” like stress of EP parameters on the skin (unpublished data).
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