Synthesis and characterization of poly(amino acid methacrylate)-stabilized diblock copolymer nano-objects
Synthesis and characterization of poly(amino acid methacrylate)-stabilized diblock copolymer nano-objects
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DOI：
10.1039/c4py01556h
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发表时间：
2015-01-01
影响因子：
4.6
通讯作者：
Armes, Steven. P.
中科院分区：
文献类型：
--
作者：
Ladmiral, Vincent;Charlot, Alexandre;Armes, Steven. P.
氨基酸是自然界最重要的组成部分之一。它们具有显著的不同性质（疏水/亲水特性、电荷密度、手性、可逆交联等）。决定了蛋白质的结构和功能。包含主链氨基酸的人工肽和蛋白质的合成对于纳米医学特别重要。然而，带有氨基酸侧链的合成聚合物更容易制备，并且可以为各种生物医学应用提供期望的性质。在此，我们描述了一种合成聚（氨基酸甲基丙烯酸酯）稳定的二嵌段共聚物纳米物体的有效途径。首先，使半胱氨酸或谷胱甘肽与市售的甲基丙烯酸酯-丙烯酸酯加合物反应以产生相应的基于氨基酸的甲基丙烯酸单体（CysMA或GSHMA）。然后通过RAFT聚合制备定义明确的水溶性大分子链转移剂（PCysMA或PGSHMA macro-CTA），然后通过甲基丙烯酸2-羟丙酯的水性RAFT分散聚合使其扩链。原位聚合诱导的自组装（比萨）发生以产生空间稳定的二嵌段共聚物纳米物体。尽管当PGSHMA用作唯一的大分子CTA时仅可以获得球形纳米颗粒，但是可以使用单独的PCysMA大分子CTA或聚（甘油单甲基丙烯酸酯）（PGMA）与PCysMA或PGSHMA大分子CTA的二元混合物来制备球体、蠕虫或囊泡。蠕虫形成软的独立的热响应凝胶，在冷却时由于蠕虫到球体的转变而经历去凝胶化。水性电泳研究表明，所有三种共聚物的形态表现出阳离子特性低于pH 3.5和阴离子特性高于pH 3.5。该pH敏感性对应于聚（氨基酸甲基丙烯酸酯）空间稳定剂链的已知行为。
Amino acids constitute one of Nature's most important building blocks. Their remarkably diverse properties (hydrophobic/hydrophilic character, charge density, chirality, reversible cross-linking etc.) dictate the structure and function of proteins. The synthesis of artificial peptides and proteins comprising main chain amino acids is of particular importance for nanomedicine. However, synthetic polymers bearing amino acid side-chains are more readily prepared and may offer desirable properties for various biomedical applications. Herein we describe an efficient route for the synthesis of poly(amino acid methacrylate)-stabilized diblock copolymer nano-objects. First, either cysteine or glutathione is reacted with a commercially available methacrylate-acrylate adduct to produce the corresponding amino acid-based methacrylic monomer (CysMA or GSHMA). Well-defined water-soluble macromolecular chain transfer agents (PCysMA or PGSHMA macro-CTAs) are then prepared via RAFT polymerization, which are then chain-extended via aqueous RAFT dispersion polymerization of 2-hydroxypropyl methacrylate. In situ polymerization- induced self-assembly (PISA) occurs to produce sterically-stabilized diblock copolymer nano-objects. Although only spherical nanoparticles could be obtained when PGSHMA was used as the sole macro-CTA, either spheres, worms or vesicles can be prepared using either PCysMA macro-CTA alone or binary mixtures of poly(glycerol monomethacrylate) (PGMA) with either PCysMA or PGSHMA macro-CTAs. The worms formed soft free-standing thermo-responsive gels that undergo degelation on cooling as a result of a worm-to-sphere transition. Aqueous electrophoresis studies indicate that all three copolymer morphologies exhibit cationic character below pH 3.5 and anionic character above pH 3.5. This pH sensitivity corresponds to the known behavior of the poly(amino acid methacrylate) steric stabilizer chains.