The role of damage in reversible electroporation optimization: theory and experiments in a vegetable model

M. MARINO; N. OLAIZ; S. MICHINSKI; P. GIUNTA; E. LUJÁN; E. GOLDBERG; A. SOBA; C. SUÁREZ; G. MARSHALL

Congreso; 3rd WCE PEF-BMFET; 2019

In electroporation (EP)-based protocols, such as in Gene Electrotransfer (GET), tissue pH-damageand ROS damage underline the EP phenomenon, however, tissue damage due to irreversible EP orthermal damage due to temperature effects may occur owing to the possible appearance of strongelectric fields in a zone very close to the electrodes. In the quest of an optimal GET protocol, theconcept of the dose-response relationship is addressed, with the objective of maximizing the desiredtreatment effect and minimizing collateral tissue damage. Previous theoretical and experimentalmeasurements for GET protocols show that a reliable dose parameter is the pulse dosage andreliable response parameters are the reversibly electroporated tissue and the unwanted damage dueto pH. Here, we extend previous results using a model of a GET protocol that combines anextension of the standard stationary EP model for predicting the reversibly electroporated tissue,and the standard Electrolytic Ablation (EA) model for predicting damage due to pH, ROS,irreversible EP and temperature. Theoretical predictions were confirmed by experimentalmeasurements in a vegetable model (potato) tuber consisting in the recording of the pH-damagedand irreversibly damaged tissue and temperature variations during the treatment, and of thereversibly electroporated tissue (blackened area) 12 hours after the treatment. It was found that anoptimal dose-response relationship in a GET protocol for different voltage to distance ratios andfixed pulse length and frequency is predicted as the critical pulse dosage yielding maximumreversibly electroporated tissue with minimum tissue damage due to pH, irreversible EP andtemperature.