Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown

The therapeutic messenger RNA strategies, such as those using small interfering RNAs, take several advantages (versatility, efficiency and selectivity) over plasmid DNA-based strategies. However, the challenge remains to f ind nanovectors capable of properly loading the genetic material, transportin...

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Autores: Sánchez-Arribas, Natalia, Velasco Rodríguez, Brenda, Aicart, Emilio, Guerrero-Martínez, Andrés, Junquera, Elena, Taboada Antelo, Pablo
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/40797
Acceso en línea:https://hdl.handle.net/10347/40797
Access Level:acceso abierto
Palabra clave:Lipid-based nanovector
Lipid nanoparticles
Gene knockdown
siRNA
Internalization route
Reactive oxygen species
3D cell spheroids
Cytotoxicity
Lamellar phase
2307 Química física
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spelling Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdownSánchez-Arribas, NataliaVelasco Rodríguez, BrendaAicart, EmilioGuerrero-Martínez, AndrésJunquera, ElenaTaboada Antelo, PabloLipid-based nanovectorLipid nanoparticlesGene knockdownsiRNAInternalization routeReactive oxygen species3D cell spheroidsCytotoxicityLamellar phase2307 Química físicaThe therapeutic messenger RNA strategies, such as those using small interfering RNAs, take several advantages (versatility, efficiency and selectivity) over plasmid DNA-based strategies. However, the challenge remains to f ind nanovectors capable of properly loading the genetic material, transporting it through troublesome environments, like a tumoral site, and delivering it into the cytoplasm of target cells. Here, lipid nanoparticles, consisting of a gemini cationic/neutral helper lipid mixture, are proposed as siRNA nanovector. Cells from cervical and brain cancer overexpressing the green fluorescent protein (GFP) were chosen to analyse the biological response as well as the efficiency and safety of the siRNA-loaded nanovector according to the cell phenotype. Flow cytometry and epifluorescence or confocal microscopy were used to follow the gene knockdown in these overexpressed cells. The effect of the nanovector on cellular proliferation was evaluated with cytotoxicity assays while their potential oxidative stress generation was determined by quantifying the generation of reactive oxygen species. To explore the mechanism of cellular uptake, different inhibitors of endocytic pathways were used during incubation with cells. Finally, nanovectors were incubated in 3D-grown cells (spheroids) to seeElsevierUniversidade de Santiago de Compostela. Instituto de Materiais (iMATUS)Universidade de Santiago de Compostela. Departamento de Física de Partículas20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/40797reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PCI2022-134981-2 OPTIMISATION OF BI-THERAPY INHIBITION OF STAPHYLOCOCCUS AUREUS IN PERSISTENT AND BACTEREMIC INFECTIONSAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PCI2022-134981-2 OPTIMISATION OF BI-THERAPY INHIBITION OF STAPHYLOCOCCUS AUREUS IN PERSISTENT AND BACTEREMIC INFECTIONSAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-123228NB-I00 DESARROLLO DE ALEACIONES DE NANOCRISTALES METALICOS COLOIDALES POR IRRADIACION LASER ULTRARRAPIDAopen accesshttp://purl.org/coar/access_right/c_abf2© 2024 The Author(s). Published by Elsevier Inchttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/407972026-06-15T12:47:27Z
dc.title.none.fl_str_mv Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
title Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
spellingShingle Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
Sánchez-Arribas, Natalia
Lipid-based nanovector
Lipid nanoparticles
Gene knockdown
siRNA
Internalization route
Reactive oxygen species
3D cell spheroids
Cytotoxicity
Lamellar phase
2307 Química física
title_short Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
title_full Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
title_fullStr Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
title_full_unstemmed Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
title_sort Lipid nanoparticles as nano-Trojan-horses for siRNA delivery and gene-knockdown
dc.creator.none.fl_str_mv Sánchez-Arribas, Natalia
Velasco Rodríguez, Brenda
Aicart, Emilio
Guerrero-Martínez, Andrés
Junquera, Elena
Taboada Antelo, Pablo
author Sánchez-Arribas, Natalia
author_facet Sánchez-Arribas, Natalia
Velasco Rodríguez, Brenda
Aicart, Emilio
Guerrero-Martínez, Andrés
Junquera, Elena
Taboada Antelo, Pablo
author_role author
author2 Velasco Rodríguez, Brenda
Aicart, Emilio
Guerrero-Martínez, Andrés
Junquera, Elena
Taboada Antelo, Pablo
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS)
Universidade de Santiago de Compostela. Departamento de Física de Partículas
dc.subject.none.fl_str_mv Lipid-based nanovector
Lipid nanoparticles
Gene knockdown
siRNA
Internalization route
Reactive oxygen species
3D cell spheroids
Cytotoxicity
Lamellar phase
2307 Química física
topic Lipid-based nanovector
Lipid nanoparticles
Gene knockdown
siRNA
Internalization route
Reactive oxygen species
3D cell spheroids
Cytotoxicity
Lamellar phase
2307 Química física
description The therapeutic messenger RNA strategies, such as those using small interfering RNAs, take several advantages (versatility, efficiency and selectivity) over plasmid DNA-based strategies. However, the challenge remains to f ind nanovectors capable of properly loading the genetic material, transporting it through troublesome environments, like a tumoral site, and delivering it into the cytoplasm of target cells. Here, lipid nanoparticles, consisting of a gemini cationic/neutral helper lipid mixture, are proposed as siRNA nanovector. Cells from cervical and brain cancer overexpressing the green fluorescent protein (GFP) were chosen to analyse the biological response as well as the efficiency and safety of the siRNA-loaded nanovector according to the cell phenotype. Flow cytometry and epifluorescence or confocal microscopy were used to follow the gene knockdown in these overexpressed cells. The effect of the nanovector on cellular proliferation was evaluated with cytotoxicity assays while their potential oxidative stress generation was determined by quantifying the generation of reactive oxygen species. To explore the mechanism of cellular uptake, different inhibitors of endocytic pathways were used during incubation with cells. Finally, nanovectors were incubated in 3D-grown cells (spheroids) to see
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-01-01
2025
2025-01-01
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/10347/40797
url https://hdl.handle.net/10347/40797
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PCI2022-134981-2 OPTIMISATION OF BI-THERAPY INHIBITION OF STAPHYLOCOCCUS AUREUS IN PERSISTENT AND BACTEREMIC INFECTIONS
Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PCI2022-134981-2 OPTIMISATION OF BI-THERAPY INHIBITION OF STAPHYLOCOCCUS AUREUS IN PERSISTENT AND BACTEREMIC INFECTIONS
Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-123228NB-I00 DESARROLLO DE ALEACIONES DE NANOCRISTALES METALICOS COLOIDALES POR IRRADIACION LASER ULTRARRAPIDA
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
© 2024 The Author(s). Published by Elsevier Inc
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
© 2024 The Author(s). Published by Elsevier Inc
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 Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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