A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study

This work reports the synthesis of a novel gemini cationic lipid that incorporates two histidine-type head groups (C3(C16His)2). Mixed with a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine (DOPE), it was used to transfect three different types of plasmid DNA: one encoding the gree...

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Detalles Bibliográficos
Autores: Martínez Negro, María, Blanco-Fernández, Laura, Tentori, Paolo M., Pérez, Lourdes, Pinazo, Aurora, Tros de Ilarduya, Conchita, Aicart Sospedra, Emilio, Junquera González, María Elena
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/12637
Acceso en línea:https://hdl.handle.net/20.500.14352/12637
Access Level:acceso abierto
Palabra clave:lipid-based gene nanocarrier
gemini cationic lipid with histidine residues
gene delivery
plasmid DNAs
transfection
cell viability
biophysical characterization
Química física (Física)
Química física (Química)
2210 Química Física
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spelling A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical StudyMartínez Negro, MaríaBlanco-Fernández, LauraTentori, Paolo M.Pérez, LourdesPinazo, AuroraTros de Ilarduya, ConchitaAicart Sospedra, EmilioJunquera González, María Elenalipid-based gene nanocarriergemini cationic lipid with histidine residuesgene deliveryplasmid DNAstransfectioncell viabilitybiophysical characterizationQuímica física (Física)Química física (Química)2210 Química FísicaThis work reports the synthesis of a novel gemini cationic lipid that incorporates two histidine-type head groups (C3(C16His)2). Mixed with a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine (DOPE), it was used to transfect three different types of plasmid DNA: one encoding the green fluorescence protein (pEGFP-C3), one encoding a luciferase (pCMV-Luc), and a therapeutic anti-tumoral agent encoding interleukin-12 (pCMV-IL12). Complementary biophysical experiments (zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and fluorescence anisotropy) and biological studies (FACS, luminometry, and cytotoxicity) of these C3(C16His)2/DOPE-pDNA lipoplexes provided vast insight into their outcomes as gene carriers. They were found to efficiently compact and protect pDNA against DNase I degradation by forming nanoaggregates of 120–290 nm in size, which were further characterized as very fluidic lamellar structures based in a sandwich-type phase, with alternating layers of mixed lipids and an aqueous monolayer where the pDNA and counterions are located. The optimum formulations of these nanoaggregates were able to transfect the pDNAs into COS-7 and HeLa cells with high cell viability, comparable or superior to that of the standard Lipo2000*. The vast amount of information collected from the in vitro studies points to this histidine-based lipid nanocarrier as a potentially interesting candidate for future in vivo studies investigating specific gene therapies.MDPIUniversidad Complutense de Madrid20182018-12-1620182018-12-16journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/12637reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/126372026-06-02T12:44:21Z
dc.title.none.fl_str_mv A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
title A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
spellingShingle A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
Martínez Negro, María
lipid-based gene nanocarrier
gemini cationic lipid with histidine residues
gene delivery
plasmid DNAs
transfection
cell viability
biophysical characterization
Química física (Física)
Química física (Química)
2210 Química Física
title_short A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
title_full A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
title_fullStr A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
title_full_unstemmed A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
title_sort A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study
dc.creator.none.fl_str_mv Martínez Negro, María
Blanco-Fernández, Laura
Tentori, Paolo M.
Pérez, Lourdes
Pinazo, Aurora
Tros de Ilarduya, Conchita
Aicart Sospedra, Emilio
Junquera González, María Elena
author Martínez Negro, María
author_facet Martínez Negro, María
Blanco-Fernández, Laura
Tentori, Paolo M.
Pérez, Lourdes
Pinazo, Aurora
Tros de Ilarduya, Conchita
Aicart Sospedra, Emilio
Junquera González, María Elena
author_role author
author2 Blanco-Fernández, Laura
Tentori, Paolo M.
Pérez, Lourdes
Pinazo, Aurora
Tros de Ilarduya, Conchita
Aicart Sospedra, Emilio
Junquera González, María Elena
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv lipid-based gene nanocarrier
gemini cationic lipid with histidine residues
gene delivery
plasmid DNAs
transfection
cell viability
biophysical characterization
Química física (Física)
Química física (Química)
2210 Química Física
topic lipid-based gene nanocarrier
gemini cationic lipid with histidine residues
gene delivery
plasmid DNAs
transfection
cell viability
biophysical characterization
Química física (Física)
Química física (Química)
2210 Química Física
description This work reports the synthesis of a novel gemini cationic lipid that incorporates two histidine-type head groups (C3(C16His)2). Mixed with a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine (DOPE), it was used to transfect three different types of plasmid DNA: one encoding the green fluorescence protein (pEGFP-C3), one encoding a luciferase (pCMV-Luc), and a therapeutic anti-tumoral agent encoding interleukin-12 (pCMV-IL12). Complementary biophysical experiments (zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and fluorescence anisotropy) and biological studies (FACS, luminometry, and cytotoxicity) of these C3(C16His)2/DOPE-pDNA lipoplexes provided vast insight into their outcomes as gene carriers. They were found to efficiently compact and protect pDNA against DNase I degradation by forming nanoaggregates of 120–290 nm in size, which were further characterized as very fluidic lamellar structures based in a sandwich-type phase, with alternating layers of mixed lipids and an aqueous monolayer where the pDNA and counterions are located. The optimum formulations of these nanoaggregates were able to transfect the pDNAs into COS-7 and HeLa cells with high cell viability, comparable or superior to that of the standard Lipo2000*. The vast amount of information collected from the in vitro studies points to this histidine-based lipid nanocarrier as a potentially interesting candidate for future in vivo studies investigating specific gene therapies.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-12-16
2018
2018-12-16
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/12637
url https://hdl.handle.net/20.500.14352/12637
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406887674380288
score 15.300724

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