Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , |
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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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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1808128343067852800 |