College of Polymer Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.
Key Laboratory of Biobased Polymer Materials, Shandong Provincial Education Department, Analyses and Testing Center, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.
Biomacromolecules. 2024 May 13;25(5):3122-3130. doi: 10.1021/acs.biomac.4c00225. Epub 2024 May 2.
Synthesis of polysaccharide--polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in -carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran--polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran--polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner ( < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran--polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.
多糖-多肽嵌段共聚物的合成是一个很有吸引力的目标，因为它们在递药应用中具有很大的潜力。受最近 -内酰胺（NCA）开环聚合（ROP）突破的启发，我们提出了一种制备葡聚糖基大分子引发剂的有效方法，并通过 NCA ROP 随后合成了葡聚糖-多肽。这是一种创建和使用天然多糖大分子引发剂进行嵌段共聚物合成的原始方法。在该策略中，线性葡聚糖非还原端的单糖 C-6 位的唯一伯醇的区域选择性（2,2,6,6-四甲基哌啶-1-基）氧基（TEMPO）氧化导致生成羧酸。然后，该基序转化为四烷基铵羧酸盐，从而生成葡聚糖大分子引发剂。该大分子引发剂引发了一系列 NCA 单体，并以可控的方式（<1.3）产生了聚合度（DP）高达 70 的多肽的葡聚糖-多肽。该策略具有几个明显的优点，包括保持原始葡聚糖骨架结构、聚合较快以及耐湿性。葡聚糖-多肽表现出有趣的自组装行为。通过动态光散射（DLS）和透射电子显微镜（TEM）研究了它们的纳米结构，并且通过调节嵌段共聚物的结构可以自组装成具有不同直径和纵横比的球形胶束和蠕虫状胶束，揭示了直径从 60nm 到 160nm 的范围。此外，这些纳米结构表现出不同的形态，包括球形胶束和蠕虫状胶束，使其能够用于递药应用。
