Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating

Detalhes bibliográficos
Autor(a) principal: Martinez Junior, Andre Miguel [UNESP]
Data de Publicação: 2022
Outros Autores: Felix Viegas de Souza, Ricchard Hallan [UNESP], Petronio, Maicon Segalla [UNESP], Martins, Grazieli Olinda [UNESP], Fernandes, Julio Cesar, Benderdour, Mohamed, Oliveira de Tiera, Vera Aparecida [UNESP], Tiera, Marcio Jose [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s40097-022-00487-0
http://hdl.handle.net/11449/218855
Resumo: The preparation of safe and efficient siRNA carriers remains a challenge that has limited the therapeutic applications of siRNA. In this study, the design of a new small interfering RNA (siRNA) carrier based on diisopropylaminoethyl-chitosan was devised for application in non-viral gene therapy. Polycations having varied proportions (11-32%) of diisopropylethylamine groups (DIPEA) and grafted with polyethylene glycol (1-3%) were synthesized and characterized. The physicochemical and biological properties of the polymers and their nanoparticles were evaluated at pH 6.3 and pH 7.4. The degrees of ionization at pH 7.4 were precisely controlled by the composition and increased from 13% for chitosan to 47% for the more substituted derivative. Nanoparticles with very low toxicities and sizes in the range of 100-200 nm, remained stable up to 24 h after their preparation in both the evaluated pHs under plasma osmolality. As probed by scanning electron and confocal microscopies, an efficient cell uptake of spherical nanoparticles mediated a TNF alpha knockdown of almost 60% in RAW 264.7 macrophages, and mRNA silence levels higher than the Lipofectamine (up to 90%) in HeLa cells. Overall, the results showed that these derivatives are promising vectors for in vivo studies under physiological conditions.
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spelling Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coatingsiRNADIPEANanoparticlesKnockdownNon-viral vectorGene therapyTNF alphaThe preparation of safe and efficient siRNA carriers remains a challenge that has limited the therapeutic applications of siRNA. In this study, the design of a new small interfering RNA (siRNA) carrier based on diisopropylaminoethyl-chitosan was devised for application in non-viral gene therapy. Polycations having varied proportions (11-32%) of diisopropylethylamine groups (DIPEA) and grafted with polyethylene glycol (1-3%) were synthesized and characterized. The physicochemical and biological properties of the polymers and their nanoparticles were evaluated at pH 6.3 and pH 7.4. The degrees of ionization at pH 7.4 were precisely controlled by the composition and increased from 13% for chitosan to 47% for the more substituted derivative. Nanoparticles with very low toxicities and sizes in the range of 100-200 nm, remained stable up to 24 h after their preparation in both the evaluated pHs under plasma osmolality. As probed by scanning electron and confocal microscopies, an efficient cell uptake of spherical nanoparticles mediated a TNF alpha knockdown of almost 60% in RAW 264.7 macrophages, and mRNA silence levels higher than the Lipofectamine (up to 90%) in HeLa cells. Overall, the results showed that these derivatives are promising vectors for in vivo studies under physiological conditions.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Ministere de l'Economie, de la Science et de l'Innovation du QuebecSao Paulo State Univ, Dept Chem & Environm Sci, UNESP, IBILCE, R Cristevao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilSao Paulo State Univ, Dept Phys, UNESP, IBILCE, Sao Jose Do Rio Preto, BrazilUniv Montreal, Orthoped Res Lab, Hop Sacre Coeur Montreal, Montreal, PQ, CanadaSao Paulo State Univ, Dept Chem & Environm Sci, UNESP, IBILCE, R Cristevao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilSao Paulo State Univ, Dept Phys, UNESP, IBILCE, Sao Jose Do Rio Preto, BrazilFAPESP: 2017/10331-5CAPES: 2017/10331-5FAPESP: 2019/27801-0FAPESP: 2015/05148-1Ministere de l'Economie, de la Science et de l'Innovation du Quebec: PSR-SIIRI-960FAPESP: 2009/53989-4SpringerUniversidade Estadual Paulista (UNESP)Univ MontrealMartinez Junior, Andre Miguel [UNESP]Felix Viegas de Souza, Ricchard Hallan [UNESP]Petronio, Maicon Segalla [UNESP]Martins, Grazieli Olinda [UNESP]Fernandes, Julio CesarBenderdour, MohamedOliveira de Tiera, Vera Aparecida [UNESP]Tiera, Marcio Jose [UNESP]2022-04-28T17:23:25Z2022-04-28T17:23:25Z2022-03-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article20http://dx.doi.org/10.1007/s40097-022-00487-0Journal Of Nanostructure In Chemistry. Heidelberg: Springer Heidelberg, 20 p., 2022.2008-9244http://hdl.handle.net/11449/21885510.1007/s40097-022-00487-0WOS:000777354100001Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal Of Nanostructure In Chemistryinfo:eu-repo/semantics/openAccess2022-04-28T17:23:25Zoai:repositorio.unesp.br:11449/218855Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:22:20.017303Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
title Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
spellingShingle Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
Martinez Junior, Andre Miguel [UNESP]
siRNA
DIPEA
Nanoparticles
Knockdown
Non-viral vector
Gene therapy
TNF alpha
title_short Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
title_full Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
title_fullStr Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
title_full_unstemmed Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
title_sort Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating
author Martinez Junior, Andre Miguel [UNESP]
author_facet Martinez Junior, Andre Miguel [UNESP]
Felix Viegas de Souza, Ricchard Hallan [UNESP]
Petronio, Maicon Segalla [UNESP]
Martins, Grazieli Olinda [UNESP]
Fernandes, Julio Cesar
Benderdour, Mohamed
Oliveira de Tiera, Vera Aparecida [UNESP]
Tiera, Marcio Jose [UNESP]
author_role author
author2 Felix Viegas de Souza, Ricchard Hallan [UNESP]
Petronio, Maicon Segalla [UNESP]
Martins, Grazieli Olinda [UNESP]
Fernandes, Julio Cesar
Benderdour, Mohamed
Oliveira de Tiera, Vera Aparecida [UNESP]
Tiera, Marcio Jose [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Univ Montreal
dc.contributor.author.fl_str_mv Martinez Junior, Andre Miguel [UNESP]
Felix Viegas de Souza, Ricchard Hallan [UNESP]
Petronio, Maicon Segalla [UNESP]
Martins, Grazieli Olinda [UNESP]
Fernandes, Julio Cesar
Benderdour, Mohamed
Oliveira de Tiera, Vera Aparecida [UNESP]
Tiera, Marcio Jose [UNESP]
dc.subject.por.fl_str_mv siRNA
DIPEA
Nanoparticles
Knockdown
Non-viral vector
Gene therapy
TNF alpha
topic siRNA
DIPEA
Nanoparticles
Knockdown
Non-viral vector
Gene therapy
TNF alpha
description The preparation of safe and efficient siRNA carriers remains a challenge that has limited the therapeutic applications of siRNA. In this study, the design of a new small interfering RNA (siRNA) carrier based on diisopropylaminoethyl-chitosan was devised for application in non-viral gene therapy. Polycations having varied proportions (11-32%) of diisopropylethylamine groups (DIPEA) and grafted with polyethylene glycol (1-3%) were synthesized and characterized. The physicochemical and biological properties of the polymers and their nanoparticles were evaluated at pH 6.3 and pH 7.4. The degrees of ionization at pH 7.4 were precisely controlled by the composition and increased from 13% for chitosan to 47% for the more substituted derivative. Nanoparticles with very low toxicities and sizes in the range of 100-200 nm, remained stable up to 24 h after their preparation in both the evaluated pHs under plasma osmolality. As probed by scanning electron and confocal microscopies, an efficient cell uptake of spherical nanoparticles mediated a TNF alpha knockdown of almost 60% in RAW 264.7 macrophages, and mRNA silence levels higher than the Lipofectamine (up to 90%) in HeLa cells. Overall, the results showed that these derivatives are promising vectors for in vivo studies under physiological conditions.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-28T17:23:25Z
2022-04-28T17:23:25Z
2022-03-31
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1007/s40097-022-00487-0
Journal Of Nanostructure In Chemistry. Heidelberg: Springer Heidelberg, 20 p., 2022.
2008-9244
http://hdl.handle.net/11449/218855
10.1007/s40097-022-00487-0
WOS:000777354100001
url http://dx.doi.org/10.1007/s40097-022-00487-0
http://hdl.handle.net/11449/218855
identifier_str_mv Journal Of Nanostructure In Chemistry. Heidelberg: Springer Heidelberg, 20 p., 2022.
2008-9244
10.1007/s40097-022-00487-0
WOS:000777354100001
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal Of Nanostructure In Chemistry
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 20
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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