Organic Chemistry Institute and Center for Soft Nanoscience, Westfälische Wilhelms-Universität Münster, Corrensstr. 40, 48149, Münster, Germany.
Macromol Rapid Commun. 2018 Jan;39(1). doi: 10.1002/marc.201700256. Epub 2017 Sep 12.
An effective and universal method for delivering structurally diverse biomolecules in vivo would greatly benefit modern drug therapy, but has yet to be discovered. Self-assembled supramolecular complexes containing vesicles of amphiphilic cyclodextrin and linker molecules with an azobenzene guest unit and a charged functionality have been established as nanoscale carriers for proteins and DNA, making use of multivalent electrostatic attraction. However, light-induced cargo release is only feasible up to a maximum net charge of the biomacromolecules. Herein, it is shown that it is possible to fine-tune macromolecular complex stability and size by addition of a competitive guest molecule that acts as a stopper, partly blocking the vesicle surface. The superior performance of arylazopyrazoles in photoisomerization compared to azobenzenes, which enables a lower surface charge density of the vesicles in the photostationary state, is also demonstrated. Both strategies allow reversible supramolecular aggregation of high molecular weight DNA (2 and 4.8 kbp).
一种有效且通用的体内传递结构多样生物分子的方法将极大地有益于现代药物治疗，但尚未被发现。自组装的超分子复合物包含具有偶氮苯客体单元和带电官能团的两亲性环糊精的囊泡和连接分子，已被确立为蛋白质和 DNA 的纳米级载体，利用多价静电吸引。然而，光诱导的货物释放仅在生物大分子的最大净电荷下才可行。本文表明，通过添加作为止动器的竞争性客体分子，可以精细调节大分子复合物的稳定性和大小，部分阻断囊泡表面。与偶氮苯相比，芳基偶氮吡唑在光异构化方面的优异性能，使其在光稳定态下的囊泡表面电荷密度更低，这也得到了证明。这两种策略都允许高相对分子质量 DNA（2 和 4.8 kbp）的可逆超分子聚集。
