Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells

Background: One of the most significant limitations that therapeutic oligonucleotides present is the development of specific and efficient delivery vectors for the internalization of nucleic acids into cells. Therefore, there is a need for the development of new transfection agents that ensure a pro...

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Autores: Delgado, Ana, Griera Farres, Rosa, Llor Brunés, Núria, López-Aguilar, Ester, Busquets i Viñas, Ma. Antonia, Noé Mata, Verónica, Ciudad i Gómez, Carlos Julián
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/194009
Acceso en línea:https://hdl.handle.net/2445/194009
Access Level:acceso abierto
Palabra clave:Oligonucleòtids
Síntesi orgànica
Oligonucleotides
Organic synthesis
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spelling Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian CellsDelgado, AnaGriera Farres, RosaLlor Brunés, NúriaLópez-Aguilar, EsterBusquets i Viñas, Ma. AntoniaNoé Mata, VerónicaCiudad i Gómez, Carlos JuliánOligonucleòtidsSíntesi orgànicaOligonucleotidesOrganic synthesisBackground: One of the most significant limitations that therapeutic oligonucleotides present is the development of specific and efficient delivery vectors for the internalization of nucleic acids into cells. Therefore, there is a need for the development of new transfection agents that ensure a proper and efficient delivery into mammalian cells. Methods: We describe the synthesis of 1,3,5-tris[(4-oelyl-1-pyridinio)methyl]benzene tribromide (TROPY) and proceeded to the validation of its binding capacity toward oligonucleotides, the internalization of DNA into the cells, the effect on cell viability, apoptosis, and its capability to transfect plasmid DNA. Results: The synthesis and chemical characterization of TROPY, which can bind DNA and transfect oligonucleotides into mammalian cells through clathrin and caveolin-mediated endocytosis, are described. Using a PPRH against the antiapoptotic survivin gene as a model, we validated that the complex TROPY-PPRH decreased cell viability in human cancer cells, increased apoptosis, and reduced survivin mRNA and protein levels. TROPY was also able to stably transfect plasmid DNA, as demonstrated by the formation of viable colonies upon the transfection of a dhfr minigene into dhfr-negative cells and the subsequent metabolic selection. Conclusions: TROPY is an efficient transfecting agent that allows the delivery of therapeutic oligonucleotides, such as PPRHs and plasmid DNA, inside mammalian cells. Keywords: therapeutic oligonucleotide; PPRH; hairpin; delivery; transfection agent; mammalian cell; cancer; cell viability; apoptosis; stable transfectionMDPI2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/194009Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/pharmaceutics15020420Pharmaceutics, 2023https://doi.org/10.3390/pharmaceutics15020420cc-by (c) Delgado, Ana et al., 2023https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1940092026-05-29T05:05:01Z
dc.title.none.fl_str_mv Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
title Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
spellingShingle Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
Delgado, Ana
Oligonucleòtids
Síntesi orgànica
Oligonucleotides
Organic synthesis
title_short Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
title_full Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
title_fullStr Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
title_full_unstemmed Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
title_sort Trioleyl Pyridinium, a Cationic Transfection Agent for the Lipofection of Therapeutic Oligonucleotides into Mammalian Cells
dc.creator.none.fl_str_mv Delgado, Ana
Griera Farres, Rosa
Llor Brunés, Núria
López-Aguilar, Ester
Busquets i Viñas, Ma. Antonia
Noé Mata, Verónica
Ciudad i Gómez, Carlos Julián
author Delgado, Ana
author_facet Delgado, Ana
Griera Farres, Rosa
Llor Brunés, Núria
López-Aguilar, Ester
Busquets i Viñas, Ma. Antonia
Noé Mata, Verónica
Ciudad i Gómez, Carlos Julián
author_role author
author2 Griera Farres, Rosa
Llor Brunés, Núria
López-Aguilar, Ester
Busquets i Viñas, Ma. Antonia
Noé Mata, Verónica
Ciudad i Gómez, Carlos Julián
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Oligonucleòtids
Síntesi orgànica
Oligonucleotides
Organic synthesis
topic Oligonucleòtids
Síntesi orgànica
Oligonucleotides
Organic synthesis
description Background: One of the most significant limitations that therapeutic oligonucleotides present is the development of specific and efficient delivery vectors for the internalization of nucleic acids into cells. Therefore, there is a need for the development of new transfection agents that ensure a proper and efficient delivery into mammalian cells. Methods: We describe the synthesis of 1,3,5-tris[(4-oelyl-1-pyridinio)methyl]benzene tribromide (TROPY) and proceeded to the validation of its binding capacity toward oligonucleotides, the internalization of DNA into the cells, the effect on cell viability, apoptosis, and its capability to transfect plasmid DNA. Results: The synthesis and chemical characterization of TROPY, which can bind DNA and transfect oligonucleotides into mammalian cells through clathrin and caveolin-mediated endocytosis, are described. Using a PPRH against the antiapoptotic survivin gene as a model, we validated that the complex TROPY-PPRH decreased cell viability in human cancer cells, increased apoptosis, and reduced survivin mRNA and protein levels. TROPY was also able to stably transfect plasmid DNA, as demonstrated by the formation of viable colonies upon the transfection of a dhfr minigene into dhfr-negative cells and the subsequent metabolic selection. Conclusions: TROPY is an efficient transfecting agent that allows the delivery of therapeutic oligonucleotides, such as PPRHs and plasmid DNA, inside mammalian cells. Keywords: therapeutic oligonucleotide; PPRH; hairpin; delivery; transfection agent; mammalian cell; cancer; cell viability; apoptosis; stable transfection
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/194009
url https://hdl.handle.net/2445/194009
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/pharmaceutics15020420
Pharmaceutics, 2023
https://doi.org/10.3390/pharmaceutics15020420
dc.rights.none.fl_str_mv cc-by (c) Delgado, Ana et al., 2023
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Delgado, Ana et al., 2023
https://creativecommons.org/licenses/by/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 Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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