State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China.
J Phys Chem B. 2013 Jul 3;117(26):7857-67. doi: 10.1021/jp312766u. Epub 2013 Jun 20.
The transfection of DNA in gene therapy largely depends on the possibility of obtaining its condensation. The details of nanoparticle formation are essential for functioning, as mediated by the diverse elements containing molecular structure, ionic strength in mediums, and condensing motivator. Here, we report two kinds of DNA condensing agents based on simple cyclic/rigid polyamine molecules, having evaluated their structural effect on nanoparticle formation. The reversible condensation-dissociation process was achieved by ion-switching, attributing to a possible condensing mechanism-competitive building of external hydrogen bonds. Using poly[(dA-dT)2] and poly[(dG-dC)2] as substrates, respectively, circular dichroism (CD) signals clearly presented dissimilar interactions between polyamines and both rich sequences, implying potential preference for G-C sequence. The presence of divalent ion Zn(2+) as an efficient motivator accelerated the achievement of DNA condensation, and an accessible schematic model was depicted to explain the promotion in detail. In addition, by comparison with the behaviors of linear polyamines, differences between condensation and aggregation were explicitly elucidated in aspects of morphology and surface charges, as well as induced condition. The present work may have the potential to reveal the precise mechanism of DNA nanoparticle formation and, in particular, be applied to gene delivery as an efficient nonviral vector.
基因治疗中的 DNA 转染在很大程度上取决于获得其浓缩的可能性。纳米颗粒形成的细节对于功能至关重要,因为其受到包含分子结构、介质中离子强度和浓缩剂的各种元素的介导。在这里,我们报告了两种基于简单环状/刚性聚胺分子的 DNA 浓缩剂,评估了它们对纳米颗粒形成的结构影响。通过离子切换实现了可逆的凝聚-解离过程,归因于可能的凝聚机制——外部氢键的竞争构建。使用聚[(dA-dT)2]和聚[(dG-dC)2]作为底物,圆二色性 (CD) 信号清楚地呈现了聚胺与富含序列之间的不同相互作用,表明对 G-C 序列有潜在的偏好。二价离子 Zn(2+)的存在作为有效的促进剂加速了 DNA 的浓缩,并且描绘了一个可访问的示意模型来详细解释这种促进作用。此外,通过与线性聚胺的行为进行比较,在形态和表面电荷以及诱导条件方面明确阐明了凝聚和聚集之间的差异。本工作可能有潜力揭示 DNA 纳米颗粒形成的确切机制,并特别应用于基因传递作为有效的非病毒载体。