Department of Chemical Engineering & Materials Science , University of Minnesota , 421 Washington Avenue SE , Minneapolis , Minnesota 55455 , United States.
Department of Chemistry , University of Minnesota , 207 Pleasant Street SE , Minneapolis , Minnesota 55455 , United States.
J Am Chem Soc. 2018 Sep 5;140(35):11101-11111. doi: 10.1021/jacs.8b06309. Epub 2018 Aug 23.
Compaction of DNA by oppositely charged nanoparticles is a fundamental phenomenon in nature and of great interest to developing therapeutics. In addition, the ability to orthogonally control the composition and structure of interpolyelectrolyte complexes is needed to develop materials for diverse applications. Herein, we systematically investigate the complexation of plasmid DNA and polymeric cationic AB and ABC micelles to explore the influence of micelle outer nonionic corona length on the colloidal stability, size, composition, and structure of the resulting "micelleplexes". The micelles were self-assembled from amphiphilic block polymers, poly(ethylene glycol)- block-poly((2-dimethylamino)ethyl methacrylate)- block-poly( n-butyl methacrylate) (PEG- b-PDMAEMA- b-PnBMA), and PDMAEMA- b-PnBMA with the same M of PDMAEMA. These spherical micelles have similar hydrodynamic radii and core sizes, but the M of the outer PEG block ranged from 0 to 10 kDa. The colloidal stability of micelleplexes as a function of stoichiometric charge ratio was assessed by turbidimetric titration and was found to dramatically improve with the addition of an outer PEG corona, even as short as 2 kDa. With the use of a combination of dynamic and static light scattering, ζ-potential, and cryogenic transmission electron microscopy, it was found that the size, composition, and structure of micelleplexes are closely correlated with the M of the PEG block. Indeed, these micelleplexes were found to adopt beads-on-a-string morphologies that resemble the general structure of chromatin, and the number of micelles per micelleplex systematically decreased with increasing PEG length. These findings demonstrate the power of polycationic micelles to condense DNA into biomimetic structures and provide a mechanistic understanding of nucleic acid complexation and of how micelle architecture affects the properties of micelleplexes, while offering an appealing strategy to control the properties of micelleplexes by tuning a single parameter.
带相反电荷的纳米粒子使 DNA 致密化是自然界中的一种基本现象，对于开发治疗方法具有重要意义。此外，需要正交控制聚电解质复合物的组成和结构，以便为各种应用开发材料。在此，我们系统地研究了质粒 DNA 与两亲性阳离子 AB 和 ABC 胶束的复合物，以探索胶束外部非离子冠长度对所得“胶束复合物”的胶体稳定性、尺寸、组成和结构的影响。这些胶束由两亲嵌段共聚物自组装而成，两亲嵌段共聚物为聚（乙二醇）-嵌段-聚（2-二甲氨基乙基甲基丙烯酸酯）-嵌段-聚（正丁基甲基丙烯酸酯）（PEG-b-PDMAEMA-b-PnBMA）和 PDMAEMA-b-PnBMA，其中 PDMAEMA 的 M 相同。这些球形胶束具有相似的流体力学半径和核尺寸，但外部 PEG 链段的 M 从 0 到 10 kDa 不等。通过光散射浊度滴定评估胶束复合物作为化学计量电荷比函数的胶体稳定性，发现即使添加短至 2 kDa 的外部 PEG 冠，胶体稳定性也会大大提高。通过使用动态和静态光散射、ζ-电位和低温透射电子显微镜的组合，发现胶束复合物的尺寸、组成和结构与 PEG 链段的 M 密切相关。实际上，这些胶束复合物被发现采用类似染色质一般结构的串珠形态，而每个胶束复合物的胶束数则随着 PEG 长度的增加而系统减少。这些发现表明阳离子胶束将 DNA 浓缩成仿生结构的能力，并提供了对核酸复合物的机制理解，以及胶束结构如何影响胶束复合物的性质，同时提供了通过调整单个参数来控制胶束复合物性质的有吸引力的策略。
