Library of cationic polymers composed of polyamines and arginine as gene transfection agents

Combinatorially synthesized materials, especially cationic polymers (CPs), with gene transfection function hold great promise in nanotechnology. However, the main limitations of the existing CPs [such as polyethylenimine (PEI), poly-l-arginine, or polyamidoamine-based dendrimers] as gene transfectio...

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Autores: Zavradashvili, Nino, Sarisozen, Can, Titvinidze, Giorgi, Otinashvili, Giuli, Kantaria, Tengiz, Tugushi, David, Puiggalí Bellalta, Jordi|||0000-0002-0640-4474, Torchilin, Vladimir P., Katsarava, Ramaz
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/173025
Acceso en línea:https://hdl.handle.net/2117/173025
https://dx.doi.org/10.1021/acsomega.8b02977
Access Level:acceso abierto
Palabra clave:Polymers
Transfection
Genetic engineering
Nanotechnology
Polímers
Enginyeria genètica
Nanotecnologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
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spelling Library of cationic polymers composed of polyamines and arginine as gene transfection agentsZavradashvili, NinoSarisozen, CanTitvinidze, GiorgiOtinashvili, GiuliKantaria, TengizTugushi, DavidPuiggalí Bellalta, Jordi|||0000-0002-0640-4474Torchilin, Vladimir P.Katsarava, RamazPolymersTransfectionGenetic engineeringNanotechnologyPolímersEnginyeria genèticaNanotecnologiaÀrees temàtiques de la UPC::Enginyeria biomèdicaCombinatorially synthesized materials, especially cationic polymers (CPs), with gene transfection function hold great promise in nanotechnology. However, the main limitations of the existing CPs [such as polyethylenimine (PEI), poly-l-arginine, or polyamidoamine-based dendrimers] as gene transfection agents are high cytotoxicity in the physiological environment. We have developed novel CPs composed of polyamines—endogeneous tetraamine spermine (Spm) and synthetically made triamine N-(2-aminoethyl)-1,3-propanediamine (Apd) for incorporating sec-amino groups and imparting PEI-like structure to the CP backbones. Naturally occurring building blocks such as amino acid arginine (R) was also used for incorporating guanidine-groups into the CPs. The cytotoxicity of resulting CPs—polyureas (PUs) and polyamides such as polysuccinamides and R-attached polymalamides was evaluated using murine and human fibroblasts and carcinoma cell lines. The cell compatibility screening revealed that the CPs made of Apd are less cytotoxic compared to Spm-based analogues. From the novel polymer library, total of six polymers were further studied for oligonucleotide (pDNA) complexation and transfection abilities. Highly water-soluble CPs formed nano-sized polyplexes with pDNA at rather low CP/pDNA weight ratios and showed less cytotoxicity and higher transfection ability compared to widely used PEI as well as commercially available transfection agents. Furthermore, new CPs showed selective transfection activity toward certain cell lines (4T1, HeLa, NIH3T3, and CCD 27SK), which is important for their potential applications in gene therapy.American Chemical Society (ACS)20192019-01-2820192019-11-25journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/173025https://dx.doi.org/10.1021/acsomega.8b02977reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivs 3.0 Spainhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/1730252026-05-27T15:37:01Z
dc.title.none.fl_str_mv Library of cationic polymers composed of polyamines and arginine as gene transfection agents
title Library of cationic polymers composed of polyamines and arginine as gene transfection agents
spellingShingle Library of cationic polymers composed of polyamines and arginine as gene transfection agents
Zavradashvili, Nino
Polymers
Transfection
Genetic engineering
Nanotechnology
Polímers
Enginyeria genètica
Nanotecnologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
title_short Library of cationic polymers composed of polyamines and arginine as gene transfection agents
title_full Library of cationic polymers composed of polyamines and arginine as gene transfection agents
title_fullStr Library of cationic polymers composed of polyamines and arginine as gene transfection agents
title_full_unstemmed Library of cationic polymers composed of polyamines and arginine as gene transfection agents
title_sort Library of cationic polymers composed of polyamines and arginine as gene transfection agents
dc.creator.none.fl_str_mv Zavradashvili, Nino
Sarisozen, Can
Titvinidze, Giorgi
Otinashvili, Giuli
Kantaria, Tengiz
Tugushi, David
Puiggalí Bellalta, Jordi|||0000-0002-0640-4474
Torchilin, Vladimir P.
Katsarava, Ramaz
author Zavradashvili, Nino
author_facet Zavradashvili, Nino
Sarisozen, Can
Titvinidze, Giorgi
Otinashvili, Giuli
Kantaria, Tengiz
Tugushi, David
Puiggalí Bellalta, Jordi|||0000-0002-0640-4474
Torchilin, Vladimir P.
Katsarava, Ramaz
author_role author
author2 Sarisozen, Can
Titvinidze, Giorgi
Otinashvili, Giuli
Kantaria, Tengiz
Tugushi, David
Puiggalí Bellalta, Jordi|||0000-0002-0640-4474
Torchilin, Vladimir P.
Katsarava, Ramaz
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Polymers
Transfection
Genetic engineering
Nanotechnology
Polímers
Enginyeria genètica
Nanotecnologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
topic Polymers
Transfection
Genetic engineering
Nanotechnology
Polímers
Enginyeria genètica
Nanotecnologia
Àrees temàtiques de la UPC::Enginyeria biomèdica
description Combinatorially synthesized materials, especially cationic polymers (CPs), with gene transfection function hold great promise in nanotechnology. However, the main limitations of the existing CPs [such as polyethylenimine (PEI), poly-l-arginine, or polyamidoamine-based dendrimers] as gene transfection agents are high cytotoxicity in the physiological environment. We have developed novel CPs composed of polyamines—endogeneous tetraamine spermine (Spm) and synthetically made triamine N-(2-aminoethyl)-1,3-propanediamine (Apd) for incorporating sec-amino groups and imparting PEI-like structure to the CP backbones. Naturally occurring building blocks such as amino acid arginine (R) was also used for incorporating guanidine-groups into the CPs. The cytotoxicity of resulting CPs—polyureas (PUs) and polyamides such as polysuccinamides and R-attached polymalamides was evaluated using murine and human fibroblasts and carcinoma cell lines. The cell compatibility screening revealed that the CPs made of Apd are less cytotoxic compared to Spm-based analogues. From the novel polymer library, total of six polymers were further studied for oligonucleotide (pDNA) complexation and transfection abilities. Highly water-soluble CPs formed nano-sized polyplexes with pDNA at rather low CP/pDNA weight ratios and showed less cytotoxicity and higher transfection ability compared to widely used PEI as well as commercially available transfection agents. Furthermore, new CPs showed selective transfection activity toward certain cell lines (4T1, HeLa, NIH3T3, and CCD 27SK), which is important for their potential applications in gene therapy.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-28
2019
2019-11-25
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/2117/173025
https://dx.doi.org/10.1021/acsomega.8b02977
url https://hdl.handle.net/2117/173025
https://dx.doi.org/10.1021/acsomega.8b02977
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
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/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
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society (ACS)
publisher.none.fl_str_mv American Chemical Society (ACS)
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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