Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency

Detalhes bibliográficos
Autor(a) principal: Picola, Isadora Pfeifer Dalla [UNESP]
Data de Publicação: 2016
Outros Autores: Shi, Qin, Fernandes, Júlio Cesar, Petrônio, Maicon Segalla [UNESP], Lima, Aline Margarete Furuyama [UNESP], de Oliveira Tiera, Vera Aparecida [UNESP], Tiera, Marcio José [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1080/09205063.2016.1225333
http://hdl.handle.net/11449/173425
Resumo: The purpose of this work was to improve the functional properties of chitosan for gene transfer by inserting phosphorylcholine (PC) and diethylaminoethyl (DEAE) groups into the main chain. A series of derivatives containing increasing contents of DEAE and a fixed content of PC groups were synthesized and characterized, aiming to evaluate the effect of these groups on the nanoparticles’ properties and the in vitro transfection efficiency. The derivatives were soluble at physiological pH levels and all derivatives were less cytotoxic than the control, the lipid lipofectamine. The obtained derivatives complexed pDNA into nanoparticles with smaller sizes and higher zeta potentials than plain chitosan. The in vitro transfection was performed with nanoparticles prepared at pH 6.3 and 7.4 and the results showed that nanoparticles prepared with derivatives containing 20% of PC groups (PC18-CH) and high degrees of substitution by DEAE (PC20-CH-DEAE100, CH-DEAE80, CH-DEAE100) displayed the better transfection efficiencies in HeLa cells, reaching relative values comparable to lipofectamine. The most effective derivative, PC18CH, was selected for complexation with siRNA and its complexes demonstrated an in vitro knockdown efficiency highly dependent on the N/P ratio. Our combined results indicated that, by means of controlled modifications, the limitations of chitosan can be overcome to obtain more effective carriers based on chitosan, and the derivatives here studied hold potential for in vivo studies.
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spelling Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiencyChitosanderivativesDNAgene therapynanoparticlesphosphorylcholinepolyplexessiRNAThe purpose of this work was to improve the functional properties of chitosan for gene transfer by inserting phosphorylcholine (PC) and diethylaminoethyl (DEAE) groups into the main chain. A series of derivatives containing increasing contents of DEAE and a fixed content of PC groups were synthesized and characterized, aiming to evaluate the effect of these groups on the nanoparticles’ properties and the in vitro transfection efficiency. The derivatives were soluble at physiological pH levels and all derivatives were less cytotoxic than the control, the lipid lipofectamine. The obtained derivatives complexed pDNA into nanoparticles with smaller sizes and higher zeta potentials than plain chitosan. The in vitro transfection was performed with nanoparticles prepared at pH 6.3 and 7.4 and the results showed that nanoparticles prepared with derivatives containing 20% of PC groups (PC18-CH) and high degrees of substitution by DEAE (PC20-CH-DEAE100, CH-DEAE80, CH-DEAE100) displayed the better transfection efficiencies in HeLa cells, reaching relative values comparable to lipofectamine. The most effective derivative, PC18CH, was selected for complexation with siRNA and its complexes demonstrated an in vitro knockdown efficiency highly dependent on the N/P ratio. Our combined results indicated that, by means of controlled modifications, the limitations of chitosan can be overcome to obtain more effective carriers based on chitosan, and the derivatives here studied hold potential for in vivo studies.Department of Physics IBILCE São Paulo State University – UNESPOrthopedic Research Laboratory Hôpital du Sacré-Cœur de Montréal Université de MontréalDepartment of Chemistry and Environmental Sciences IBILCE São Paulo State University – UNESPDepartment of Physics IBILCE São Paulo State University – UNESPDepartment of Chemistry and Environmental Sciences IBILCE São Paulo State University – UNESPUniversidade Estadual Paulista (Unesp)Université de MontréalPicola, Isadora Pfeifer Dalla [UNESP]Shi, QinFernandes, Júlio CesarPetrônio, Maicon Segalla [UNESP]Lima, Aline Margarete Furuyama [UNESP]de Oliveira Tiera, Vera Aparecida [UNESP]Tiera, Marcio José [UNESP]2018-12-11T17:05:23Z2018-12-11T17:05:23Z2016-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1611-1630application/pdfhttp://dx.doi.org/10.1080/09205063.2016.1225333Journal of Biomaterials Science, Polymer Edition, v. 27, n. 16, p. 1611-1630, 2016.1568-56240920-5063http://hdl.handle.net/11449/17342510.1080/09205063.2016.12253332-s2.0-849846903372-s2.0-84984690337.pdf8796747160088337Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Biomaterials Science, Polymer Edition0,5370,537info:eu-repo/semantics/openAccess2023-10-08T06:02:04Zoai:repositorio.unesp.br:11449/173425Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:18:08.179929Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
title Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
spellingShingle Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
Picola, Isadora Pfeifer Dalla [UNESP]
Chitosan
derivatives
DNA
gene therapy
nanoparticles
phosphorylcholine
polyplexes
siRNA
title_short Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
title_full Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
title_fullStr Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
title_full_unstemmed Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
title_sort Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
author Picola, Isadora Pfeifer Dalla [UNESP]
author_facet Picola, Isadora Pfeifer Dalla [UNESP]
Shi, Qin
Fernandes, Júlio Cesar
Petrônio, Maicon Segalla [UNESP]
Lima, Aline Margarete Furuyama [UNESP]
de Oliveira Tiera, Vera Aparecida [UNESP]
Tiera, Marcio José [UNESP]
author_role author
author2 Shi, Qin
Fernandes, Júlio Cesar
Petrônio, Maicon Segalla [UNESP]
Lima, Aline Margarete Furuyama [UNESP]
de Oliveira Tiera, Vera Aparecida [UNESP]
Tiera, Marcio José [UNESP]
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Université de Montréal
dc.contributor.author.fl_str_mv Picola, Isadora Pfeifer Dalla [UNESP]
Shi, Qin
Fernandes, Júlio Cesar
Petrônio, Maicon Segalla [UNESP]
Lima, Aline Margarete Furuyama [UNESP]
de Oliveira Tiera, Vera Aparecida [UNESP]
Tiera, Marcio José [UNESP]
dc.subject.por.fl_str_mv Chitosan
derivatives
DNA
gene therapy
nanoparticles
phosphorylcholine
polyplexes
siRNA
topic Chitosan
derivatives
DNA
gene therapy
nanoparticles
phosphorylcholine
polyplexes
siRNA
description The purpose of this work was to improve the functional properties of chitosan for gene transfer by inserting phosphorylcholine (PC) and diethylaminoethyl (DEAE) groups into the main chain. A series of derivatives containing increasing contents of DEAE and a fixed content of PC groups were synthesized and characterized, aiming to evaluate the effect of these groups on the nanoparticles’ properties and the in vitro transfection efficiency. The derivatives were soluble at physiological pH levels and all derivatives were less cytotoxic than the control, the lipid lipofectamine. The obtained derivatives complexed pDNA into nanoparticles with smaller sizes and higher zeta potentials than plain chitosan. The in vitro transfection was performed with nanoparticles prepared at pH 6.3 and 7.4 and the results showed that nanoparticles prepared with derivatives containing 20% of PC groups (PC18-CH) and high degrees of substitution by DEAE (PC20-CH-DEAE100, CH-DEAE80, CH-DEAE100) displayed the better transfection efficiencies in HeLa cells, reaching relative values comparable to lipofectamine. The most effective derivative, PC18CH, was selected for complexation with siRNA and its complexes demonstrated an in vitro knockdown efficiency highly dependent on the N/P ratio. Our combined results indicated that, by means of controlled modifications, the limitations of chitosan can be overcome to obtain more effective carriers based on chitosan, and the derivatives here studied hold potential for in vivo studies.
publishDate 2016
dc.date.none.fl_str_mv 2016-11-01
2018-12-11T17:05:23Z
2018-12-11T17:05:23Z
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/10.1080/09205063.2016.1225333
Journal of Biomaterials Science, Polymer Edition, v. 27, n. 16, p. 1611-1630, 2016.
1568-5624
0920-5063
http://hdl.handle.net/11449/173425
10.1080/09205063.2016.1225333
2-s2.0-84984690337
2-s2.0-84984690337.pdf
8796747160088337
url http://dx.doi.org/10.1080/09205063.2016.1225333
http://hdl.handle.net/11449/173425
identifier_str_mv Journal of Biomaterials Science, Polymer Edition, v. 27, n. 16, p. 1611-1630, 2016.
1568-5624
0920-5063
10.1080/09205063.2016.1225333
2-s2.0-84984690337
2-s2.0-84984690337.pdf
8796747160088337
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Biomaterials Science, Polymer Edition
0,537
0,537
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1611-1630
application/pdf
dc.source.none.fl_str_mv Scopus
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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