Petkau-Milroy Katja, Ianiro Alessandro, Ahn Melanie M L, Magana Jose Rodrigo, Vleugels Marle E J, Lamers Brigitte A G, Tuinier Remco, Voets Ilja K, Palmans Anja R A, Meijer E W
ACS Macro Lett. 2020 Jan 21;9(1):38-42. doi: 10.1021/acsmacrolett.9b00814. Epub 2019 Dec 12.
Access to versatile and stable nanostructures formed by the self-assembly of block copolymers in water is essential for biomedical applications. These applications require control over the stability, morphology, and size of the formed nanostructures. Here, we study the self-assembly in water of a library of fully discrete and sequence-controlled AB-type block co-oligomers (BCOs) of oligo(l-lactic acid)--oligo(ethylene glycol). In this series, we eliminate all the inherent uncertainty associated with molar mass, ratio, and compositional dispersity, but vary the ratio between the water-soluble and water-insoluble parts. The BCO library is designed in such a way that vesicles, spherical micelles, and cylindrical micelles are generated in solution, hereby covering a variety of common morphologies. With the help of self-consistent field (SCF) computations, the thermodynamic structures in water are predicted for all structures. The morphologies formed were experimentally analyzed using a combination of calorimetry and scattering techniques. When comparing the experimentally found structures with those predicted, we find an excellent agreement. Intriguingly, calorimetry showed the presence of crystallized l-lactic acid (LLA) units in the bilayer of the lamellar forming BCO. Despite this crystallinity, there is no mismatch between the predicted and observed bilayer thicknesses upon self-assembly in water. In this case, phase separation driven by the hydrophobic LLA block coincides with crystallization, resulting in stable morphologies. Thus, SCF guided library design and sample preparation can lead toward robust formulations of nanoparticles.
在生物医学应用中，获得由嵌段共聚物在水中自组装形成的通用且稳定的纳米结构至关重要。这些应用需要控制所形成纳米结构的稳定性、形态和尺寸。在此，我们研究了一系列完全离散且序列可控的聚（L-乳酸）-聚（乙二醇）AB型嵌段共低聚物（BCOs）在水中的自组装。在这个系列中，我们消除了与摩尔质量、比例和组成分散性相关的所有固有不确定性，但改变了水溶性部分和水不溶性部分之间的比例。BCO文库的设计方式使得在溶液中产生囊泡、球形胶束和圆柱形胶束，从而涵盖了各种常见形态。借助自洽场（SCF）计算，预测了所有结构在水中的热力学结构。使用量热法和散射技术相结合的方法对形成的形态进行了实验分析。当将实验发现的结构与预测的结构进行比较时，我们发现两者非常吻合。有趣的是，量热法显示在形成层状的BCO的双层中存在结晶的L-乳酸（LLA）单元。尽管存在这种结晶性，但在水中自组装时预测的和观察到的双层厚度之间没有不匹配。在这种情况下，由疏水性LLA嵌段驱动的相分离与结晶同时发生，从而产生稳定的形态。因此，SCF指导的文库设计和样品制备可以通向纳米颗粒的稳健配方。
