A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid

The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (D...

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Detalles Bibliográficos
Autores: Martínez Negro, María, Sánchez Arribas, Natalia, Guerrero Martínez, Andrés, Moyá, María Luisa, Tros de Ilarduya, Conchita, Mendicuti, Francisco, Aicart Sospedra, Emilio, Junquera González, María Elena
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/8281
Acceso en línea:https://hdl.handle.net/20.500.14352/8281
Access Level:acceso abierto
Palabra clave:lysine-derived cationic lipid
plasmid DNA
lipoplex
transfection
protection
compaction
gene delivery
multilamellar aggregates
molecular dynamics
Química física (Física)
Química física (Química)
2210 Química Física
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oai_identifier_str oai:docta.ucm.es:20.500.14352/8281
network_acronym_str ES
network_name_str España
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spelling A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic LipidMartínez Negro, MaríaSánchez Arribas, NataliaGuerrero Martínez, AndrésMoyá, María LuisaTros de Ilarduya, ConchitaMendicuti, FranciscoAicart Sospedra, EmilioJunquera González, María Elenalysine-derived cationic lipidplasmid DNAlipoplextransfectionprotectioncompactiongene deliverymultilamellar aggregatesmolecular dynamicsQuímica física (Física)Química física (Química)2210 Química FísicaThe insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*.MDPIUniversidad Complutense de Madrid20192019-11-2720192019-11-27journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/8281reponame: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:20.500.14352/82812026-06-02T12:44:21Z
dc.title.none.fl_str_mv A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
title A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
spellingShingle A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
Martínez Negro, María
lysine-derived cationic lipid
plasmid DNA
lipoplex
transfection
protection
compaction
gene delivery
multilamellar aggregates
molecular dynamics
Química física (Física)
Química física (Química)
2210 Química Física
title_short A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
title_full A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
title_fullStr A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
title_full_unstemmed A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
title_sort A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
dc.creator.none.fl_str_mv Martínez Negro, María
Sánchez Arribas, Natalia
Guerrero Martínez, Andrés
Moyá, María Luisa
Tros de Ilarduya, Conchita
Mendicuti, Francisco
Aicart Sospedra, Emilio
Junquera González, María Elena
author Martínez Negro, María
author_facet Martínez Negro, María
Sánchez Arribas, Natalia
Guerrero Martínez, Andrés
Moyá, María Luisa
Tros de Ilarduya, Conchita
Mendicuti, Francisco
Aicart Sospedra, Emilio
Junquera González, María Elena
author_role author
author2 Sánchez Arribas, Natalia
Guerrero Martínez, Andrés
Moyá, María Luisa
Tros de Ilarduya, Conchita
Mendicuti, Francisco
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 lysine-derived cationic lipid
plasmid DNA
lipoplex
transfection
protection
compaction
gene delivery
multilamellar aggregates
molecular dynamics
Química física (Física)
Química física (Química)
2210 Química Física
topic lysine-derived cationic lipid
plasmid DNA
lipoplex
transfection
protection
compaction
gene delivery
multilamellar aggregates
molecular dynamics
Química física (Física)
Química física (Química)
2210 Química Física
description The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-11-27
2019
2019-11-27
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/20.500.14352/8281
url https://hdl.handle.net/20.500.14352/8281
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_ 1869403737596887040
score 15,301603

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