Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12

Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-1...

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Autores: Sánchez Arribas, Natalia, Martínez Negro, María, Aicart, Clara, Tros de Ilarduya, Conchita, Aicart Sospedra, Emilio, Guerrero Martínez, Andrés, Junquera González, María Elena
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/108994
Acceso en línea:https://hdl.handle.net/20.500.14352/108994
Access Level:acceso abierto
Palabra clave:544
577.1
Non-viral gene delivery
Gemini cationic lipid
Transfection
Protein corona
Interleukin-12
Pro-inflammatory cytokine
Química física (Química)
Bioquímica (Química)
2307 Química Física
2302.26 Bioquímica Física
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oai_identifier_str oai:docta.ucm.es:20.500.14352/108994
network_acronym_str ES
network_name_str España
repository_id_str
spelling Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12Sánchez Arribas, NataliaMartínez Negro, MaríaAicart, ClaraTros de Ilarduya, ConchitaAicart Sospedra, EmilioGuerrero Martínez, AndrésJunquera González, María Elena544577.1Non-viral gene deliveryGemini cationic lipidTransfectionProtein coronaInterleukin-12Pro-inflammatory cytokineQuímica física (Química)Bioquímica (Química)2307 Química Física2302.26 Bioquímica FísicaAmple evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.MDPIUniversidad Complutense de Madrid20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/108994reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available RTI2018-095844-B-I00Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available RTI2018-097609-B-C22Ministerio de Educación y Ciencia Not available UCMA05-33-010Ministerio de Educación y Ciencia Not available GR2019open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1089942026-06-02T12:44:21Z
dc.title.none.fl_str_mv Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
title Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
spellingShingle Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
Sánchez Arribas, Natalia
544
577.1
Non-viral gene delivery
Gemini cationic lipid
Transfection
Protein corona
Interleukin-12
Pro-inflammatory cytokine
Química física (Química)
Bioquímica (Química)
2307 Química Física
2302.26 Bioquímica Física
title_short Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
title_full Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
title_fullStr Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
title_full_unstemmed Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
title_sort Gemini cationic lipid-type nanovectors suitable for the transfection of therapeutic plasmid DNA encoding for pro-inflammatory cytokine interleukin-12
dc.creator.none.fl_str_mv Sánchez Arribas, Natalia
Martínez Negro, María
Aicart, Clara
Tros de Ilarduya, Conchita
Aicart Sospedra, Emilio
Guerrero Martínez, Andrés
Junquera González, María Elena
author Sánchez Arribas, Natalia
author_facet Sánchez Arribas, Natalia
Martínez Negro, María
Aicart, Clara
Tros de Ilarduya, Conchita
Aicart Sospedra, Emilio
Guerrero Martínez, Andrés
Junquera González, María Elena
author_role author
author2 Martínez Negro, María
Aicart, Clara
Tros de Ilarduya, Conchita
Aicart Sospedra, Emilio
Guerrero Martínez, Andrés
Junquera González, María Elena
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 544
577.1
Non-viral gene delivery
Gemini cationic lipid
Transfection
Protein corona
Interleukin-12
Pro-inflammatory cytokine
Química física (Química)
Bioquímica (Química)
2307 Química Física
2302.26 Bioquímica Física
topic 544
577.1
Non-viral gene delivery
Gemini cationic lipid
Transfection
Protein corona
Interleukin-12
Pro-inflammatory cytokine
Química física (Química)
Bioquímica (Química)
2307 Química Física
2302.26 Bioquímica Física
description Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/108994
url https://hdl.handle.net/20.500.14352/108994
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available RTI2018-095844-B-I00
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available RTI2018-097609-B-C22
Ministerio de Educación y Ciencia Not available UCMA05-33-010
Ministerio de Educación y Ciencia Not available GR2019
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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_ 1869423024090906624
score 15.81155

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