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学科主题: 高分子化学
题名: Novel symmetric amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) with high plasmid DNA binding affinity as a biodegradable gene carrier
其他题名: 作为生物降解载体的具有高质粒DNA结合力的新型不对称两亲树枝状聚赖氨酸共聚乳酸共聚树枝状聚赖氨酸
作者: Li Y(李洋) ; Cui L(崔亮) ; Li QB(李巧波) ; Jia L(贾林) ; Xu YH(徐宇虹) ; Fang Q(房强) ; Cao AM(曹阿民)
通讯作者: 曹阿民
刊名: Biomacromolecules
发表日期: 2007
卷: 8, 期:5, 页:1409-1416
收录类别: SCI
部门归属: 中科院上海有机所; 海交通大学
英文摘要: This study communicates the molecular design, preparation, and biological application of novel symmetric amphiphilic polycationic dendritic poly(L-lysine)-b- poly(L-lactide)-b-dendritic poly(L-lysine) D-2-LLA(15)-D-2 bearing two two-generation poly(L-lysine) PLL dendrons D-2 and a central hydrophobic biodegradable poly(L-lactide) block LLA(15). First, an amino-protected precursor of L-1- OH was designed and synthesized and was further employed to prepare L-1-LLA(15) with an organic 4-(dimethylamino)-pyridine-mediated living-ring-opening polymerization of L-lactide. Subsequently, the hydroxy end-capped L-1-LLA(15) was coupled to synthesize a new triblock L(1)LLA(15)- L-1 with two one-generation amino-protected PLL dendrons L-1. Furthermore, with a repeated trifluoroaceticacid-mediated amino deprotection-protection cycle, new amphiphilic triblock D-2-LLA(15)-D-2 was successfully prepared. By means of NMR, mass spectrometry, and gel permeation chromatography, these synthetic precursors and final amphiphilic product were characterized to bear well- defined triblock structures. In addition, this synthesized amphiphilic triblock polycationic macromolecule was applied as a new polycationic plasmid DNA carrier, and its DNA binding affinity was examined via an agarose electrophoresis and a fluorescence titration assay along with two important references of hydrophilic dendritic D-2-HEX-D-2 and double- hydrophilic D-2-PEG- 4K-D-2 bearing the same two D-2 dendrons; much enhanced DNA binding affinity was interestingly revealed for the new amphiphilic structural D-2-LLA(15)-D-2. Moreover, the assembled polyplex microparticles of plasmid DNA/polycationic carrier were further analyzed by dynamic light scattering and transmission electron microscopy, indicating their averaged nanoparticle size around 150-200 nm. As for the cytotoxicity of the new D-2- LLA(15)-D-2, MTT assays were conducted with a human hepatocellular carcinoma cell line (SMMC-7721), indicating a very low cytotoxicity as compared with commercial linear PLL-23K and PEI-2K, and a DNase I degradation of the assembled polyplex particles was also done in the HBS buffer solution to evaluate their stabilities. Finally, employing the new amphiphilic D-2-LLA(15)-D-2 as gene carrier, in vitro gene transfection experiments were conducted with the SMMC-7721 cell line, indicating a transfection efficiency increase of at least 10 times higher than that of the naked plasmid DNA under a N/P charge ratio of 10. Therefore, these interesting results may provide a new possible way to construct efficient polycationic macromolecular gene carriers with low toxicity and less expensive low-generation PLL dendrons.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000246413600007
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/22930
Appears in Collections:高分子材料研究室_期刊论文

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Recommended Citation:
Li Y,Cui L,Li QB,et al. Novel symmetric amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) with high plasmid DNA binding affinity as a biodegradable gene carrier[J]. Biomacromolecules,2007,8(5):1409-1416.
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