The Development of Novel Flexible Electrode Arrays for the Electrochemotherapy of Solid Tumour Tissue. (Potential for Endoscopic Treatment of Inaccessible Cancers)

摘要

Therapeutic “ electroporation” involves application of electric fields to target cells/tissues, thereby rendering their cell membranes transiently porous, thus making feasible the cellular uptake and efficacy of previously impermeant and ineffective therapeutic agents. The objectives of this research are a) the development of flexible electrode arrays for incorporation into microsystem endoscopic devices, and b) the assessment of their efficacy in delivering selected genetic and pharmaceutical anticancer therapies. Gold electrodes were fabricated on flexible polyimide substrates following predictive modeling and simulation of electric fields using FEMLAB software. Subsequent assessment of electroporation efficiency in-vitro involved 1) enumeration of viable tumour cells after delivery of electric pulses and exposure to low concentrations of bleomycin, otherwise known as electrochemotherapy 2) Efficacy of gene delivery by detection of emitted green fluorescence by cells after electroporation with the pEGFP plasmid and 3) In-vivo efficacy of electrochemotherapy in a variety of human solid tumour masses in nude mouse models (xenografts). The flexible electrode system was found to be successful for electrical delivery of plasmids and drugs in-vitro and in-vivo. We found in-vivo complete regression of prostate, colon, oesophageal, and renal cancers with reduced growth rates for fibrosarcoma and breast cell lines. These flexible electrodes are suitable for electrochemotherapy or gene therapy to solid tumours masses and may be fabricated for application to the treatment of some cancers in humans by transcutaneous or endoscopic delivery systems.