Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

Jing-Jing Yao, Yong-Zhong Du, Hong Yuan, Jian You, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of ChinaAbstract: Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the g...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yao JJ, Du YZ, Yuan H, You J, Hu FQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2b773ca52b034382981410a275442bb7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2b773ca52b034382981410a275442bb7
record_format	dspace
spelling	oai:doaj.org-article:2b773ca52b034382981410a275442bb72021-12-02T02:32:06ZEfficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles1178-2013https://doaj.org/article/2b773ca52b034382981410a275442bb72014-06-01T00:00:00Zhttp://www.dovepress.com/efficient-gene-delivery-system-mediated-by-cis-aconitate-modified-chit-a17252https://doaj.org/toc/1178-2013 Jing-Jing Yao, Yong-Zhong Du, Hong Yuan, Jian You, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of ChinaAbstract: Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA). The CA-CSO-SA micelles had a similar size, critical micelle concentration, and morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA) to form nanocomplexes. However, the DNA binding ability of CA-CSO-SA was slightly reduced compared with that of CSO-SA. The transfection efficiency mediated by CA-CSO-SA/pDNA against HEK-293 cells reached up to 37%, and was much higher than that of CSO-SA/pDNA (16%). Although the cis-aconitate modification reduced cellular uptake kinetics in the initial stages, the total amount of cellular uptake tended to be the same after 24 hours of incubation. An endocytosis inhibition experiment showed that the internalization mechanism of CA-CSO-SA/pDNA in HEK-293 cells was mainly via clathrin-mediated endocytosis, as well as caveolae-mediated endocytosis and macropinocytosis. Observation of intracellular trafficking indicated that the CSO-SA/pDNA complexes were trapped in endolysosomes, but CA-CSO-SA/pDNA was more widely distributed in the cytosol. This study suggests that modification with cis-aconitate improves the transfection efficiency of CSO-SA/pDNA.Keywords: chitosan-g-stearic acid, cis-aconitate, micelles, transfection efficiency, intracellular traffickingYao JJDu YZYuan HYou JHu FQDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2993-3003 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yao JJ Du YZ Yuan H You J Hu FQ Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
description	Jing-Jing Yao, Yong-Zhong Du, Hong Yuan, Jian You, Fu-Qiang HuCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of ChinaAbstract: Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA). The CA-CSO-SA micelles had a similar size, critical micelle concentration, and morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA) to form nanocomplexes. However, the DNA binding ability of CA-CSO-SA was slightly reduced compared with that of CSO-SA. The transfection efficiency mediated by CA-CSO-SA/pDNA against HEK-293 cells reached up to 37%, and was much higher than that of CSO-SA/pDNA (16%). Although the cis-aconitate modification reduced cellular uptake kinetics in the initial stages, the total amount of cellular uptake tended to be the same after 24 hours of incubation. An endocytosis inhibition experiment showed that the internalization mechanism of CA-CSO-SA/pDNA in HEK-293 cells was mainly via clathrin-mediated endocytosis, as well as caveolae-mediated endocytosis and macropinocytosis. Observation of intracellular trafficking indicated that the CSO-SA/pDNA complexes were trapped in endolysosomes, but CA-CSO-SA/pDNA was more widely distributed in the cytosol. This study suggests that modification with cis-aconitate improves the transfection efficiency of CSO-SA/pDNA.Keywords: chitosan-g-stearic acid, cis-aconitate, micelles, transfection efficiency, intracellular trafficking
format	article
author	Yao JJ Du YZ Yuan H You J Hu FQ
author_facet	Yao JJ Du YZ Yuan H You J Hu FQ
author_sort	Yao JJ
title	Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
title_short	Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
title_full	Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
title_fullStr	Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
title_full_unstemmed	Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
title_sort	efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/2b773ca52b034382981410a275442bb7
work_keys_str_mv	AT yaojj efficientgenedeliverysystemmediatedbycisaconitatemodifiedchitosangstearicacidmicelles AT duyz efficientgenedeliverysystemmediatedbycisaconitatemodifiedchitosangstearicacidmicelles AT yuanh efficientgenedeliverysystemmediatedbycisaconitatemodifiedchitosangstearicacidmicelles AT youj efficientgenedeliverysystemmediatedbycisaconitatemodifiedchitosangstearicacidmicelles AT hufq efficientgenedeliverysystemmediatedbycisaconitatemodifiedchitosangstearicacidmicelles
_version_	1718402399481102336

Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

Ejemplares similares