Engineering self‐assembled superstructures through complexation of plasmid DNA (pDNA) and single‐isomer nanometric size macromolecules (molecular nanoparticles) is a promising strategy for gene delivery. Notably, the functionality and overall architecture of the vector can be precisely molded at the atomic level by chemical tailoring, thereby enabling unprecedented opportunities for structure/self‐assembling/pDNA delivery relationship studies. Beyond this notion, by judiciously preorganizing the functional elements in cyclodextrin (CD)‐based molecular nanoparticles through covalent dimerization, here we demonstrate that the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from spherical to ellipsoidal, rod‐type, or worm‐like nanoparticles, which makes it possible to gain understanding of their shape‐dependent transfection properties. The experimental findings are in agreement with a shift from chelate to cross‐linking interactions on going from primary‐face‐ to secondary‐face‐linked CD dimers, the pDNA partner acting as an active payload and as a template. Most interestingly, the transfection efficiency in different cells was shown to be differently impacted by modifications of the CDplex morphology, which has led to the identification of an optimal prototype for tissue‐selective DNA delivery to the spleen in vivo.

中文翻译：

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通过分子载体设计的DNA-环糊精纳米颗粒形态的质粒模板控制，可有效传递基因。

通过质粒DNA（pDNA）和单异构体纳米大小的大分子（分子纳米颗粒）的复合工程化自组装的上层建筑是一种有前途的基因传递策略。值得注意的是，可以通过化学剪裁在原子水平上精确模制载体的功能和整体架构，从而为结构/自组装/ pDNA传递关系研究提供前所未有的机会。超越此概念，通过共价二聚化明智地预组织基于环糊精（CD）的分子纳米颗粒中的功能元素，在这里我们证明可以调节所得纳米复合物（CDplexes）的形态，从球形到椭圆形，棒状或蠕虫状的纳米粒子，这使得有可能了解其形状依赖性转染特性。实验结果与从螯合相互作用转变为交联相互作用（从初级面连接到次级面连接的CD二聚体）相一致，pDNA伴侣充当了有效负载和模板。最有趣的是，不同的细胞转染效率受到CDplex形态修饰的不同影响，从而确定了将组织选择性DNA输送至体内的最佳原型。