Max Mousseron Institute on Biomolecules, UMR CNRS 5247, University Montpellier I, 34093 Montpellier, France.
Nanoscale. 2013 Oct 7;5(19):9010-7. doi: 10.1039/c3nr02899b. Epub 2013 Aug 2.
A series of poly(ethylene glycol)-polylactide-poly(ethylene glycol) (PEG-PLA-PEG) triblock copolymers with symmetric or asymmetric chain structures were synthesized by combination of ring-opening polymerization and copper-catalyzed click chemistry. The resulting copolymers were used to prepare self-assembled aggregates by dialysis. Various architectures such as nanotubes, polymersomes and spherical micelles were observed from transmission electron microscopy (TEM), cryo-TEM and atomic force microscopy (AFM) measurements. The formation of diverse aggregates is explained by modeling from the angle of both geometry and thermodynamics. From the angle of geometry, a "blob" model based on the Daoud-Cotton model for star polymers is proposed to describe the aggregate structures and structural changes with copolymer composition and molar mass. In fact, the copolymer chains extend in aqueous medium to form single layer polymersomes to minimize the system's free energy if one of the two PEG blocks is short enough. The curvature of polymersomes is dependent on the chain structure of copolymers, especially on the length of PLA blocks. A constant branch number of aggregates (f) is thus required to preserve the morphology of polymersomes. Meanwhile, the aggregation number (N(agg)) determined from the thermodynamics of self-assembly is roughly proportional to the total length of polymer chains. Comparing f to N(agg), the aggregates take the form of polymersomes if N(agg) ≈ f, and change to nanotubes if N(agg) > f to conform to the limits from both curvature and aggregation number. The length of nanotubes is mainly determined by the difference between N(agg) and f. However, the hollow structure becomes unstable when both PEG segments are too long, and the aggregates eventually collapse to yield spherical micelles. Therefore, this work gives new insights into the self-assembly behavior of PEG-PLA-PEG triblock copolymers in aqueous solution which present great interest for biomedical and pharmaceutical applications.
采用开环聚合和铜催化点击化学相结合的方法合成了一系列具有对称或不对称链结构的聚（乙二醇）-聚（乳酸）-聚（乙二醇）（PEG-PLA-PEG）三嵌段共聚物。所得共聚物通过透析法用于制备自组装聚集体。从透射电子显微镜（TEM）、冷冻 TEM 和原子力显微镜（AFM）测量中观察到各种结构，如纳米管、聚合物囊泡和球形胶束。从几何形状和热力学两个角度对不同聚集态的形成进行了建模解释。从几何形状的角度，提出了一种基于星型聚合物的 Daoud-Cotton 模型的“小球”模型，用于描述聚合物体积相转变与共聚物组成和分子量的关系。实际上，如果两个 PEG 嵌段之一足够短，共聚物链在水介质中伸展形成单层聚合物囊泡，以最小化体系的自由能。聚合物囊泡的曲率取决于共聚物的链结构，尤其是 PLA 嵌段的长度。因此，为了保持聚合物囊泡的形态，需要有一个恒定的支化数（f）。同时，从自组装热力学确定的聚集数（N(agg)）大致与聚合物链的总长度成正比。比较 f 与 N(agg)，如果 N(agg)≈f，聚合物体积相转变为聚合物囊泡，如果 N(agg)>f，则转变为纳米管，以符合曲率和聚集数的限制。纳米管的长度主要取决于 N(agg)和 f 之间的差异。然而，当两个 PEG 段过长时，纳米管的中空结构变得不稳定，聚合物体积相最终坍塌形成球形胶束。因此，这项工作为 PEG-PLA-PEG 三嵌段共聚物在水溶液中的自组装行为提供了新的见解，这对生物医学和制药应用具有重要意义。
