Département de Chimie, Université de Montréal , C.P. 6128, Succ. Centre-ville, Montréal, Quebec H3C 3J7, Canada.
Biomacromolecules. 2014 May 12;15(5):1837-44. doi: 10.1021/bm5002262. Epub 2014 Apr 24.
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-based micelles show promise as a versatile and potent platform for cancer chemotherapy.
一系列由寡聚乙二醇和胆酸侧基组成的嵌段和无规共聚物通过其降冰片烯衍生物的开环易位聚合合成。这些嵌段和无规共聚物被设计为具有相似的分子量和共聚单体比；这两种类型的共聚物在水溶液中均表现出热敏性，具有相似的浊点。共聚物在水中自组装成胶束，如动态光散射和透射电子显微镜所示。嵌段共聚物形成的胶束的水动力直径大得多，在浊点以下 20 至 54°C 的范围内表现出宽而逐渐的收缩，而无规共聚物形成的胶束尺寸较小，但在相同温度范围内略有膨胀。基于体外药物释放研究，分别有 78%和 24%的紫杉醇（PTX）在 24 小时内从由嵌段和无规共聚物自组装形成的胶束中释放出来。由嵌段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。基于胆酸的胶束作为一种多功能、有效的癌症化疗平台具有广阔的前景。
