pH fronts and tissue natural buffer interaction in gene electrotransfer protocols

Autores
Marino, M; Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Suárez, Cecilia Ana; Michinski, Sebastián Diego; Marshall, Guillermo Ricardo
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Marino, M. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Signori, Emanuela. Consiglio Nazionale delle Ricerche; Italia
Fil: Maglietti, Felipe Horacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Suárez, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Michinski, Sebastián Diego. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Materia
Electrochemotherapy
Electrolytic Ablation
Gene Electrotransfer
Irreversible Electroporation
Ph Front Tracking
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/57660
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/57660
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling pH fronts and tissue natural buffer interaction in gene electrotransfer protocolsMarino, MOlaiz, Nahuel ManuelSignori, EmanuelaMaglietti, Felipe HoracioSuárez, Cecilia AnaMichinski, Sebastián DiegoMarshall, Guillermo RicardoElectrochemotherapyElectrolytic AblationGene ElectrotransferIrreversible ElectroporationPh Front Trackinghttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Gene 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.Fil: Marino, M. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Signori, Emanuela. Consiglio Nazionale delle Ricerche; ItaliaFil: Maglietti, Felipe Horacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Suárez, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Michinski, Sebastián Diego. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaPergamon-Elsevier Science Ltd2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/57660Marino, M; Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Suárez, Cecilia Ana; et al.; pH fronts and tissue natural buffer interaction in gene electrotransfer protocols; Pergamon-Elsevier Science Ltd; Electrochimica Acta; 255; 11-2017; 463-4710013-4686CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.electacta.2017.09.021info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:38Zoai:ri.conicet.gov.ar:11336/57660instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:38.78CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
title pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
spellingShingle pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
Marino, M
Electrochemotherapy
Electrolytic Ablation
Gene Electrotransfer
Irreversible Electroporation
Ph Front Tracking
title_short pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
title_full pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
title_fullStr pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
title_full_unstemmed pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
title_sort pH fronts and tissue natural buffer interaction in gene electrotransfer protocols
dc.creator.none.fl_str_mv Marino, M
Olaiz, Nahuel Manuel
Signori, Emanuela
Maglietti, Felipe Horacio
Suárez, Cecilia Ana
Michinski, Sebastián Diego
Marshall, Guillermo Ricardo
author Marino, M
author_facet Marino, M
Olaiz, Nahuel Manuel
Signori, Emanuela
Maglietti, Felipe Horacio
Suárez, Cecilia Ana
Michinski, Sebastián Diego
Marshall, Guillermo Ricardo
author_role author
author2 Olaiz, Nahuel Manuel
Signori, Emanuela
Maglietti, Felipe Horacio
Suárez, Cecilia Ana
Michinski, Sebastián Diego
Marshall, Guillermo Ricardo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Electrochemotherapy
Electrolytic Ablation
Gene Electrotransfer
Irreversible Electroporation
Ph Front Tracking
topic Electrochemotherapy
Electrolytic Ablation
Gene Electrotransfer
Irreversible Electroporation
Ph Front Tracking
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Marino, M. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Signori, Emanuela. Consiglio Nazionale delle Ricerche; Italia
Fil: Maglietti, Felipe Horacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Suárez, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Michinski, Sebastián Diego. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/57660
Marino, M; Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Suárez, Cecilia Ana; et al.; pH fronts and tissue natural buffer interaction in gene electrotransfer protocols; Pergamon-Elsevier Science Ltd; Electrochimica Acta; 255; 11-2017; 463-471
0013-4686
CONICET Digital
CONICET
url http://hdl.handle.net/11336/57660
identifier_str_mv Marino, M; Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Suárez, Cecilia Ana; et al.; pH fronts and tissue natural buffer interaction in gene electrotransfer protocols; Pergamon-Elsevier Science Ltd; Electrochimica Acta; 255; 11-2017; 463-471
0013-4686
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.electacta.2017.09.021
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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