Barts and the London School of Medicine and Dentistry, Queen Mary, University of London , 4 Newark Street, London, E1 2AT, United Kingdom.
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University , 20520 Turku, Finland.
Biomacromolecules. 2017 Dec 11;18(12):4121-4132. doi: 10.1021/acs.biomac.7b01175. Epub 2017 Oct 25.
Polymer brush-functionalized nanomaterials offer interesting features for the design of gene delivery vectors as their physicochemical and structural properties can be designed independently of the chemistry, size and shape of the nanomaterial core. However, little is known of the parameters regulating the adsorption and infiltration of DNA molecules at the surface of positively charged polymer brushes, despite the importance of such processes for gene delivery. Here we investigate the role of the molecular environment (e.g., pH, type of buffer, concentration) on the interactions between plasmid DNA and positively charged poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes using a combination of light scattering, electrophoretic light scattering, in situ ellipsometry, and surface plasmon resonance. We show that the conformation of swollen PDMAEMA brushes is modulated by the surrounding buffer and that this impacts strongly on the ability of such brushes and nanomaterials based on these coatings to complex DNA molecules. In turn, the levels of transfection efficiency measured correlate with changes in brush conformation and DNA binding. Therefore, this work demonstrates the importance of molecular design of polymer brushes to control DNA complexation and release in order to optimize the performance of polymer brush-functionalized nanomaterials for gene delivery applications.
聚合物刷功能化纳米材料为基因传递载体的设计提供了有趣的特性，因为它们的物理化学和结构性质可以独立于纳米材料核心的化学性质、大小和形状来设计。然而，尽管这些过程对于基因传递很重要，但对于调节正电荷聚合物刷表面上 DNA 分子吸附和渗透的参数知之甚少。在这里，我们使用光散射、电泳光散射、原位椭圆测量法和表面等离子体共振的组合，研究了分子环境（例如 pH 值、缓冲液类型、浓度）对质粒 DNA 与正电荷聚（二甲基氨基乙基甲基丙烯酸酯）（PDMAEMA）刷之间相互作用的影响。我们表明，膨胀的 PDMAEMA 刷的构象受周围缓冲液的调节，这强烈影响这些刷以及基于这些涂层的纳米材料与 DNA 分子复合的能力。反过来，测量的转染效率水平与刷构象和 DNA 结合的变化相关。因此，这项工作证明了聚合物刷的分子设计对于控制 DNA 复合和释放以优化聚合物刷功能化纳米材料在基因传递应用中的性能的重要性。
