School of Chemistry , University of Bristol , Bristol BS8 1TS , United Kingdom.
School of Physics , University of Bristol , Tyndall Avenue , Bristol BS8 1TL , United Kingdom.
J Am Chem Soc. 2019 Dec 4;141(48):19088-19098. doi: 10.1021/jacs.9b09885. Epub 2019 Nov 20.
Fiber-like micelles based on biodegradable and biocompatible polymers exhibit considerable promise for applications in nanomedicine, but until recently no convenient methods were available to prepare samples with uniform and controllable dimensions and spatial control of functionality. "Living" crystallization-driven self-assembly (CDSA) is a seeded growth method of growing importance for the preparation of uniform 1D and 2D core-shell nanoparticles from a range of crystallizable polymeric amphiphiles. However, in the case of poly(l-lactide) (PLLA), arguably the most widely utilized biodegradable polymer as the crystallizable core-forming block, the controlled formation of uniform fiber-like structures over a substantial range of lengths by "living" CDSA has been a major challenge. Herein, we demonstrate that via simple modulation of the solvent conditions via the addition of trifluoroethanol (TFE), DMSO, DMF and acetone, uniform fiber-like nanoparticles from PLLA diblock copolymers with controlled lengths up to 1 μm can be prepared. The probable mechanism involves improved unimer solvation by a reduction of hydrogen bonding interactions among PLLA chains. We provide evidence that this minimizes undesirable unimer aggregation which otherwise favors self-nucleation that competes with epitaxial crystallization from seed termini. This approach has also allowed the formation of well-defined segmented block comicelles with PLLA cores via the sequential seeded-growth of PLLA block copolymers with different corona-forming blocks.
基于可生物降解和生物相容聚合物的纤维状胶束在纳米医学应用中具有很大的应用前景，但直到最近，还没有方便的方法来制备具有均匀可控尺寸和功能空间控制的样品。“活性”结晶驱动自组装（CDSA）是一种种子生长方法，对于从各种结晶性两亲聚合物制备均匀的 1D 和 2D 核壳纳米粒子具有越来越重要的意义。然而，在聚（L-丙交酯）（PLLA）的情况下，PLLA 可以说是作为结晶核形成嵌段的最广泛使用的可生物降解聚合物，通过“活性”CDSA 控制形成均匀的纤维状结构的长度范围很大一直是一个主要挑战。在此，我们证明通过简单地通过添加三氟乙醇（TFE）、DMSO、DMF 和丙酮来调节溶剂条件，可以制备出具有受控长度高达 1μm 的均匀纤维状纳米粒子的 PLLA 两亲嵌段共聚物。可能的机制涉及通过减少 PLLA 链之间的氢键相互作用来改善单体的溶解。我们提供的证据表明，这最大限度地减少了不希望的单体聚集，否则有利于自成核，从而与种子末端的外延结晶竞争。通过顺序生长具有不同冠形成嵌段的 PLLA 嵌段共聚物，这种方法还允许形成具有 PLLA 核的定义明确的分段块状胶束。
