Hyperbranched cationic amylopectin derivatives for gene delivery.
Hyperbranched cationic amylopectin derivatives for gene delivery.
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DOI：
10.1016/j.biomaterials.2012.03.014
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发表时间：
2012-06
期刊：
影响因子：
14
通讯作者：
Yanfang Zhou;Bing Yang;X. Ren;Zhenzhen Liu;Zheng Deng;Luming Chen;Yu-bin Deng;Li‐Ming Zhang
中科院分区：
文献类型：
--
作者：
Yanfang Zhou;Bing Yang;X. Ren;Zhenzhen Liu;Zheng Deng;Luming Chen;Yu-bin Deng;Li‐Ming Zhang
用N，N‘-甲酰基二咪唑活化法在室温下合成了一系列与1，2-乙二胺、二乙烯三胺和3-二甲氨基-1-丙胺残基偶联的超支化阳离子支链淀粉衍生物，命名为EDA-AMP、DETA-AMP和DMAPA-AMP。通过红外光谱和核磁共振氢谱对其结构进行了表征，并通过酸碱滴定评价了它们的缓冲性能。与支化聚乙烯亚胺(BPEI)相比，支链淀粉衍生物具有更好的血液相容性和更低的细胞毒性。原子力显微镜和光学显微镜证实支链淀粉衍生物对红细胞的损伤低于bPEI。支链淀粉衍生物能与质粒DNA结合并缩合，形成100~300 nm的复合体。所形成的复合体在293T细胞中的转染率高于在A549细胞中的转染率。Western印迹、流式细胞仪和Hoechst染色分析表明，DMAPA-Amp衍生物介导的Forkhead box O1基因在293T细胞中的蛋白表达高于EDA-Amp和DETA-Amp衍生物。在这些数据的基础上，支链淀粉衍生物显示出作为非病毒基因载体的潜力。
A series of hyperbranched cationic amylopectin derivatives conjugated with 1,2-ethylenediamine, diethylenetriamine and 3-(dimethylamino)-1-propylamine residues, named as EDA-Amp, DETA-Amp and DMAPA-Amp, were synthesized by the N,N’-carbonyldiimidazole activation method at room temperature. Their structures were characterized by FTIR and1H NMR analyses, and their buffering capability was assessed by acid-base titration. The amylopectin derivatives exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI) in the hemolysis and MTT assays. Atomic force microscopy and optical microscopy confirmed that the amylopectin derivatives exhibited lower damage for erythrocytes than bPEI. The amylopectin derivatives could bind and condense plasmid DNA (pDNA) to form the complexes with the size ranging from 100 to 300 nm. The resultant complexes showed higher transfection efficiency in 293T cells than in A549 cells. The DMAPA-Amp derivative-mediated gene transfection for Forkhead box O1 exhibited higher protein expression than that of the EDA-Amp and DETA-Amp derivatives in 293T cells, which was analyzed by western blot, flow cytometry and Hoechst staining assay. On the basis of these data, amylopectin derivatives exhibit potential as nonviral gene vectors.