pH fronts and tissue natural buffer interaction in gene electrotransfer protocols

Gene electrotransfer (GET) protocols, based on the introduction into the cells of genes encoding immunomodulatory molecules, constitute a safe and powerful strategy for inducing an immune response against cancer. But GET efficiency can be significantly affected by damage due to the products of elect...

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Autor principal: Marino, M.
Otros Autores: Olaiz, N., Signori, E., Maglietti, F., Suárez, C., Michinski, S., Marshall, Guillermo Ricardo
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Elsevier Ltd 2017
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100 1 |a Marino, M. 
245 1 0 |a pH fronts and tissue natural buffer interaction in gene electrotransfer protocols 
260 |b Elsevier Ltd  |c 2017 
270 1 0 |m Marshall, G.; Consejo Nacional de Investigaciones Científicas y TécnicasArgentina; email: marshalg@retina.ar 
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504 |a Marino, M., Olaiz, N., Signori, E., Maglietti, F., Suarez, C., Colombo, L., Turjanski, P., Marshall, G., (2014), https://www.researchgate.net/profile/Nahuel_Olaiz/publication/266317861., Tissue damage in vaccination protocols based on electroporation: pH fronts and tissue natural buffering. Book of Proceedings from 14th International Conference on Progress In Vaccination against Cancer PIVAC-14, 24-26-September 2014, Rome, Italy, abstract 22, page 43. Poster available from; Wong, T.K., Neumann, E., Electric field mediated gene transfer (1982) Biochemical and biophysical research communications, 107 (2), pp. 584-587 
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504 |a Maglietti, F., Michinski, S., Olaiz, N., Castro, M., Suárez, C., Marshall, G., The role of Ph fronts in tissue electroporation based treatments (2013) PLoS ONE, 8 (11), pp. 1-8 
504 |a Olaiz, N., Signori, E., Maglietti, F., Soba, A., Suárez, C., Turjanski, P., Michinski, S., Marshall, G., Tissue damage modeling in gene electrotransfer: The role of pH (2014) Bioelectrochemistry 100 (October 2015), pp. 105-111 
504 |a Nilsson, E., Berendson, J., Fontes, E., Electrochemical treatment of tumours: a simplified mathematical model (1999) J Electroanal Chem, 460 (1-2), pp. 88-99 
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506 |2 openaire  |e Política editorial 
520 3 |a Gene electrotransfer (GET) protocols, based on the introduction into the cells of genes encoding immunomodulatory molecules, constitute a safe and powerful strategy for inducing an immune response against cancer. But GET efficiency can be significantly affected by damage due to the products of electrolysis, in particular, pH fronts. To elucidate the role of pH fronts and damage in GET efficiency we present an analysis of the pH fronts-tissue natural buffer interaction through a theoretical model using the Nernst-Planck equations for ion transport assuming a tissue with a bicarbonate buffering system and its validation with experimental measurements. pH front-buffer interaction measurements unveil a remarkable behavior tuned by pulse length and frequency: during the ON pulse critical pH front trajectories (pH=8.5 or 5.5) jump forward, during the OFF pulse, they recede due to tissue natural buffer attenuation. Theory shows that they are intimately related to ion transport mode: during the ON pulse, ion transport is mainly governed by migration and trajectories jump forward in time; during the OFF pulse, migration ceases, ion transport is governed solely by diffusion and trajectories recede due to buffer attenuation. Experiments and theory show that regardless of the presence of buffer attenuation, pH fronts remain during several minutes in a non-physiological state after the treatment. These results suggest that regions enclosed by pH fronts trajectories (thus subjected to non-physiological pH values during a sufficiently long time) may be subjected to plasmid damage during a GET treatment. Ways to minimize this effect, thus optimizing GET efficiency are suggested. © 2017  |l eng 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: 2014/17 
536 |a Detalles de la financiación: TD 1104 
536 |a Detalles de la financiación: PIP 379/12 
536 |a Detalles de la financiación: M. Marino and F. Maglietti have a scholarship from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Argentina; N. Olaiz, G. Marshall, and S. Michinski are researchers at CONICET; E. Signori is a researcher at CNR-Rome, Italy. This work was supported by grants from CONICET PIP 379/12, Universidad de Buenos Aires UBACyT 2014/17 and the International European Cooperation in Science and Technology (COST Action TD 1104). E. Signori was partially supported by CNR-Short Term Mobility fellowship 2016. The founders had no role in the study, design, data collection, analysis, decision to publish, or preparation of the manuscript. 
593 |a Laboratorio de Sistemas Complejos, Departamento de Computación,Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina 
593 |a Instituto de Física del Plasma, Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina 
593 |a Laboratory of Molecular Pathology and Experimental Oncology, CNR-IFT, Rome, Italy 
593 |a Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina 
650 1 7 |2 spines  |a GENES 
650 1 7 |2 spines  |a PH 
690 1 0 |a ELECTROCHEMOTHERAPY 
690 1 0 |a ELECTROLYTIC ABLATION 
690 1 0 |a GENE ELECTROTRANSFER 
690 1 0 |a IRREVERSIBLE ELECTROPORATION 
690 1 0 |a PH FRONT TRACKING 
690 1 0 |a EFFICIENCY 
690 1 0 |a GENE ENCODING 
690 1 0 |a IONS 
690 1 0 |a PHYSIOLOGY 
690 1 0 |a TRAJECTORIES 
690 1 0 |a ELECTROCHEMOTHERAPY 
690 1 0 |a ELECTROPORATION 
690 1 0 |a ELECTROTRANSFER 
690 1 0 |a FRONT TRACKING 
690 1 0 |a NERNST-PLANCK EQUATIONS 
690 1 0 |a PHYSIOLOGICAL PH 
690 1 0 |a PHYSIOLOGICAL STATE 
690 1 0 |a THEORETICAL MODELING 
690 1 0 |a TISSUE 
700 1 |a Olaiz, N. 
700 1 |a Signori, E. 
700 1 |a Maglietti, F. 
700 1 |a Suárez, C. 
700 1 |a Michinski, S. 
700 1 |a Marshall, Guillermo Ricardo 
773 0 |d Elsevier Ltd, 2017  |g v. 255  |h pp. 463-471  |p Electrochim Acta  |x 00134686  |w (AR-BaUEN)CENRE-12  |t Electrochimica Acta 
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