Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein Strasse, D-35032 Marburg, Germany.
Biomacromolecules. 2011 Oct 10;12(10):3684-91. doi: 10.1021/bm2009125. Epub 2011 Sep 2.
The synthesis of a photo-triggered biocompatible drug delivery system on the basis of coumarin-functionalized block copolymers is reported. The coumarin-functionalized block copolymers poly(ethylene oxide)-b-poly(n-butyl methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy]coumarin)) (PEO-b-P(BMA- co-CMA)) were synthesized via atom transfer radical polymerization (ATRP). The micelle-drug conjugates were made by covalent bonding of anticancer drug 5-fluorouracil (5-FU) to the coumarin under UV irradiation at wavelength >310 nm. These micelle-drug conjugates possessed spherical morphology with diameters of 70 nm from TEM images. In vitro drug release experiments showed the controlled release of anticancer drug 5-FU from the micelle-drug conjugates under UV irradiation (254 nm). These micelle-drug conjugates also showed excellent biocompatibility by the in vitro cytotoxicity experiments. The results suggest that these micelle-drug conjugates could be a promising candidate for the delivery of anticancer agents with low side effects on normal cells and excellent therapeutic efficacy to cancer cells.
报道了一种基于香豆素功能化嵌段共聚物的光触发型生物相容药物传递系统的合成。通过原子转移自由基聚合(ATRP)合成了香豆素功能化嵌段共聚物聚(氧化乙烯)-b-聚(正丁基甲基丙烯酸酯-co-4-甲基-[7-(甲基丙烯酰氧基乙氧基)香豆素])(PEO-b-P(BMA-co-CMA))。将抗癌药物 5-氟尿嘧啶(5-FU)在 310nm 以上的紫外光照射下与香豆素共价键合,制备了胶束-药物偶联物。从 TEM 图像可知,这些胶束-药物偶联物具有 70nm 的球形形态。体外药物释放实验表明,在紫外光(254nm)照射下,抗癌药物 5-FU 从胶束-药物偶联物中得到控制释放。通过体外细胞毒性实验,这些胶束-药物偶联物也表现出良好的生物相容性。结果表明,这些胶束-药物偶联物可能是一种有前途的候选药物,用于输送抗癌药物,对正常细胞的副作用低,对癌细胞的治疗效果好。