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学科主题药学
A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid
Chen, Cheng-Jun1; Zhao, Zhi-Xia1; Wang, Jian-Cheng1; Zhao, En-Yu1; Gao, Ling-Yan1; Zhou, Shu-Feng2; Liu, Xiao-Yan1; Lu, Wan-Liang1; Zhang, Qiang1
关键词small interfering RNA poly(amido amine)s siRNA ternary complex mixing order hyaluronic acid siRNA delivery
刊名INTERNATIONAL JOURNAL OF NANOMEDICINE
2012
DOI10.2147/IJN.S32676
7页:3837-3849
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Nanoscience & Nanotechnology ; Pharmacology & Pharmacy
研究领域[WOS]Science & Technology - Other Topics ; Pharmacology & Pharmacy
关键词[WOS]BREAST-CANCER CELLS ; GENE DELIVERY ; RNA INTERFERENCE ; POLY(AMIDO AMINE)S ; SIRNA DELIVERY ; THERAPY ; DESIGN ; CD44 ; POLYETHYLENIMINE ; HYALURONAN
英文摘要

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 > mixing order I > 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.

语种英语
WOS记录号WOS:000306506200001
项目编号2007CB935800 ; 2009CB930300 ; 2009ZX09310-001 ; 81072597 ; 7112089 ; BMU20110268 ; BMU20110263
资助机构National Basic Research Program of China (973 Program) ; Program for New Drug RD ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Ministry of Education
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60716
专题北京大学药学院_药剂学系
作者单位1.Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Univ S Florida, Coll Pharm, Dept Pharmaceut Sci, Tampa, FL USA
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Chen, Cheng-Jun,Zhao, Zhi-Xia,Wang, Jian-Cheng,et al. A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2012,7:3837-3849.
APA Chen, Cheng-Jun.,Zhao, Zhi-Xia.,Wang, Jian-Cheng.,Zhao, En-Yu.,Gao, Ling-Yan.,...&Zhang, Qiang.(2012).A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid.INTERNATIONAL JOURNAL OF NANOMEDICINE,7,3837-3849.
MLA Chen, Cheng-Jun,et al."A comparative study of three ternary complexes prepared in different mixing orders of siRNA/redox-responsive hyperbranched poly (amido amine)/hyaluronic acid".INTERNATIONAL JOURNAL OF NANOMEDICINE 7(2012):3837-3849.
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