Reversible DNA Condensation Induced by a Tetranuclear Nickel(II) Complex

被引:46
作者
Dong, Xindian [2 ]
Wang, Xiaoyong [1 ]
He, Yafeng [2 ]
Yu, Zhen [2 ]
Lin, Miaoxin [2 ]
Zhang, Changli [2 ]
Wang, Jing [1 ]
Song, Yajie [1 ]
Zhang, Yangmiao [2 ]
Liu, Zhipeng [2 ]
Li, Yizhi [2 ]
Guo, Zijian [2 ]
机构
[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China
[2] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Coordinat Chem, Nanjing 210093, Peoples R China
基金
中国国家自然科学基金;
关键词
DNA; electrostatic interactions; gene therapy; nickel; nonviral vector; COPPER(II) COMPLEXES; GENE-THERAPY; TRANSFECTION; CURVATURE; STABILITY; CLEAVAGE; DELIVERY; CHITOSAN; VECTORS; BINDING;
D O I
10.1002/chem.201001457
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
DNA condensing agents play a critical role in gene therapy. A tetra-nuclear nickel(II) complex, [Ni-4(II)(L-2H)(H2O)(6)(CH3CH2OH)(2)]center dot 6NO(3) (L=3,3',5,5'-tetrakis{[(2-hydroxyethyl)- (pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4'-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P2(1)/n, a=10.291(9), b= 24.15(2), c=13.896(11) angstrom, and beta=98.175(13)degrees. The DNA condensation induced by the complex has been investigated by means of UV/Vis spectroscopy; fluorescence spectroscopy, circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, gel electrophoresis assay, and zeta potential. analysis. The complex interacts strongly with DNA through electrostatic attraction and induces its condensation into globular nanoparticles at low concentration. The release of DNA from its compact state has been achieved using the chelator ethylenediaminetetraacetic acid (EDTA) for the first time. Other essential properties, such as DNA cleavage inactivity and biocompatibility, have also been examined in vitro. In general, the complex satisfies the requirements of a gene vector in all of these respects.
引用
收藏
页码:14181 / 14189
页数:9
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