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首页> 美国卫生研究院文献>ACS AuthorChoice >Block and Random Copolymers Bearing Cholic Acid andOligo(ethylene glycol) Pendant Groups: Aggregation Thermosensitivityand Drug Loading
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Block and Random Copolymers Bearing Cholic Acid andOligo(ethylene glycol) Pendant Groups: Aggregation Thermosensitivityand Drug Loading

机译：含胆酸和丙烯酸的嵌段和无规共聚物寡聚（乙二醇）链坠基团：聚集热敏性和药物装载

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摘要

A series of block and random copolymers consisting of oligo(ethylene glycol) and cholic acid pendant groups were synthesized via ring-opening metathesis polymerization of their norbornene derivatives. These block and random copolymers were designed to have similar molecular weights and comonomer ratios; both types of copolymers showed thermosensitivity in aqueous solutions with similar cloud points. The copolymers self-assembled into micelles in water as shown by dynamic light scattering and transmission electron microscopy. The hydrodynamic diameter of the micelles formed by the block copolymer is much larger and exhibited a broad and gradual shrinkage from 20 to 54 °C below its cloud point, while the micelles formed by the random copolymers are smaller in size but exhibited some swelling in the same temperature range. Based on in vitro drug release studies, 78% and 24% paclitaxel (PTX) were released in 24 h from micelles self-assembled by the block and random copolymers, respectively. PTX-loaded micelles formed by the block and random copolymers exhibited apparent antitumor efficacy toward the ovarian cancer cells with a particularly low half-maximal inhibitory concentration (IC50) of 27.4 and 40.2 ng/mL, respectively. Cholic acid-basedmicelles show promise as a versatile and potent platform for cancerchemotherapy.
机译：通过降冰片烯衍生物的开环易位聚合，合成了由低聚乙二醇和胆酸侧基组成的一系列嵌段和无规共聚物。这些嵌段共聚物和无规共聚物被设计为具有相似的分子量和共聚单体比率。两种类型的共聚物在具有相似浊点的水溶液中均表现出热敏性。如动态光散射和透射电子显微镜所示，该共聚物在水中自组装成胶束。由嵌段共聚物形成的胶束的流体力学直径要大得多，并且在低于其浊点的20至54°C范围内呈现出广泛的逐渐收缩，而由无规共聚物形成的胶束的尺寸较小，但在胶束中却显示出一些溶胀。相同的温度范围。根据体外药物释放研究，在24小时内分别由嵌段共聚物和无规共聚物自组装的胶束释放了78％和24％的紫杉醇（PTX）。由嵌段共聚物和无规共聚物形成的载有PTX的胶束对卵巢癌细胞表现出明显的抗肿瘤功效，其半最大抑制浓度（IC50）分别为27.4和40.2 ng / mL，特别低。基于胆酸胶束显示出有望成为癌症的多功能和有效平台化学疗法。

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