A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid

Cheng-Jun Chen,1 Zhi-Xia Zhao,1 Jian-Cheng Wang,1 En-Yu Zhao,1 Ling-Yan Gao,1 Shu-Feng Zhou,2 Xiao-Yan Liu,1 Wan-Liang Lu,1 Qiang Zhang11State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People&rsq...

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Autores principales:	Chen CJ, Zhao ZX, Wang JC, Zhao EY, Gao LY, Zhou SF, Liu XY, Lu WL, Zhang Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c17ea8cf46d34b429de40387ed6248b6
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spelling	oai:doaj.org-article:c17ea8cf46d34b429de40387ed6248b62021-12-02T02:35:14ZA comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid1176-91141178-2013https://doaj.org/article/c17ea8cf46d34b429de40387ed6248b62012-07-01T00:00:00Zhttp://www.dovepress.com/a-comparative-study-of-three-ternary-complexes-prepared-in-different-m-a10446https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Cheng-Jun Chen,1 Zhi-Xia Zhao,1 Jian-Cheng Wang,1 En-Yu Zhao,1 Ling-Yan Gao,1 Shu-Feng Zhou,2 Xiao-Yan Liu,1 Wan-Liang Lu,1 Qiang Zhang11State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People&rsquo;s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USAAbstract: In this study, a novel redox-responsive hyperbranched poly(amido amine) (named PCD) was synthesized and used as a cationic polymer to form a ternary complex with small interfering RNA (siRNA) and hyaluronic acid (HA) for siRNA delivery. Here, it is hypothesized that different mixing orders result in different assembly structures, which may affect the siRNA delivery efficiency. To investigate the effects of mixing orders on siRNA delivery efficiency in two human breast cancer cell lines, three ternary complexes with different mixing orders of siRNA/PCD/HA were prepared and characterized: mixing order I (initially prepared siRNA/PCD binary complex further coated by negatively charged HA), mixing order II (initially prepared HA/PCD binary complex further incubated with siRNA), and mixing order III (initially prepared siRNA/HA mixture further electrostatically compacted by positively charged PCD). With an optimized siRNA/PCD/HA charge ratio of 1/20/16, the particle sizes and zeta potentials of these ternary complexes were 124.8 nm and 27.3 mV (mixing order I), 147.5 nm and 29.9 mV (mixing order II), and 128.8 nm and 19.4 mV (mixing order III). Also, the effects on stability, cellular uptake, and gene silencing efficiency of siRNA formulated in ternary complexes with different mixing orders were investigated. The results showed that mixing orders I and III displayed better siRNA transfection and protection than mixing order II in human breast cancer MCF-7 and MDA-MB-231 cells. More interesting, at the siRNA/PCD/HA charge ratio of 1/20/16, the gene silencing effects on vascular endothelial growth factor expression in MDA-MB-231 cells were as follows: mixing order III &gt; mixing order I &gt; mixing order II. Based on these results, a likely explanation for the difference in functionality dependent on mixing orders is the formation of different assembly structures. These results may help future optimization of siRNA ternary complexes for achieving better delivery efficiencies, especially for target-specific siRNA delivery to cells with HA receptor overexpression.Keywords: small interfering RNA, poly(amido amine)s, siRNA ternary complex, mixing order, hyaluronic acid, siRNA deliveryChen CJZhao ZXWang JCZhao EYGao LYZhou SFLiu XYLu WLZhang QDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3837-3849 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen CJ Zhao ZX Wang JC Zhao EY Gao LY Zhou SF Liu XY Lu WL Zhang Q A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
description	Cheng-Jun Chen,1 Zhi-Xia Zhao,1 Jian-Cheng Wang,1 En-Yu Zhao,1 Ling-Yan Gao,1 Shu-Feng Zhou,2 Xiao-Yan Liu,1 Wan-Liang Lu,1 Qiang Zhang11State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People&rsquo;s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USAAbstract: In this study, a novel redox-responsive hyperbranched poly(amido amine) (named PCD) was synthesized and used as a cationic polymer to form a ternary complex with small interfering RNA (siRNA) and hyaluronic acid (HA) for siRNA delivery. Here, it is hypothesized that different mixing orders result in different assembly structures, which may affect the siRNA delivery efficiency. To investigate the effects of mixing orders on siRNA delivery efficiency in two human breast cancer cell lines, three ternary complexes with different mixing orders of siRNA/PCD/HA were prepared and characterized: mixing order I (initially prepared siRNA/PCD binary complex further coated by negatively charged HA), mixing order II (initially prepared HA/PCD binary complex further incubated with siRNA), and mixing order III (initially prepared siRNA/HA mixture further electrostatically compacted by positively charged PCD). With an optimized siRNA/PCD/HA charge ratio of 1/20/16, the particle sizes and zeta potentials of these ternary complexes were 124.8 nm and 27.3 mV (mixing order I), 147.5 nm and 29.9 mV (mixing order II), and 128.8 nm and 19.4 mV (mixing order III). Also, the effects on stability, cellular uptake, and gene silencing efficiency of siRNA formulated in ternary complexes with different mixing orders were investigated. The results showed that mixing orders I and III displayed better siRNA transfection and protection than mixing order II in human breast cancer MCF-7 and MDA-MB-231 cells. More interesting, at the siRNA/PCD/HA charge ratio of 1/20/16, the gene silencing effects on vascular endothelial growth factor expression in MDA-MB-231 cells were as follows: mixing order III &gt; mixing order I &gt; mixing order II. Based on these results, a likely explanation for the difference in functionality dependent on mixing orders is the formation of different assembly structures. These results may help future optimization of siRNA ternary complexes for achieving better delivery efficiencies, especially for target-specific siRNA delivery to cells with HA receptor overexpression.Keywords: small interfering RNA, poly(amido amine)s, siRNA ternary complex, mixing order, hyaluronic acid, siRNA delivery
format	article
author	Chen CJ Zhao ZX Wang JC Zhao EY Gao LY Zhou SF Liu XY Lu WL Zhang Q
author_facet	Chen CJ Zhao ZX Wang JC Zhao EY Gao LY Zhou SF Liu XY Lu WL Zhang Q
author_sort	Chen CJ
title	A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
title_short	A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
title_full	A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
title_fullStr	A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
title_full_unstemmed	A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
title_sort	comparative study of three ternary complexes prepared in different mixing orders of sirna/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/c17ea8cf46d34b429de40387ed6248b6
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A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid

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