Zhang Zhiping, Huey Lee Sie, Feng Si-Shen
Department of Chemical & Biomolecular Engineering, Faculty of Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore.
Biomaterials. 2007 Apr;28(10):1889-99. doi: 10.1016/j.biomaterials.2006.12.018. Epub 2007 Jan 2.
Doxorubicin-loaded nanoparticles (NPs) of vitamin E TPGS-folate (TPGS-FOL) conjugate and doxorubicin-poly(lactide-co-glycolide)-vitamin E TPGS (DOX-PLGA-TPGS) conjugate were prepared by the solvent extraction/evaporation method for targeted chemotherapy of folate-receptor rich tumors. X-ray photoelectron spectroscopy demonstrated that folate was distributed on the NP surface while the drug molecules were entrapped in the NP matrix. The NPs were found of approximately 350nm diameter and exhibited a biphasic pattern of in vitro drug release. The cell uptake of the fluorescent NPs and the cell viability of the drug formulated in the NPs were quantitatively investigated, which were found dependent on the content of targeting TPGS-FOL conjugate. The NPs of 50% TPGS-FOL showed cellular uptake by MCF-7 cells 1.5 times higher and by C6 cells 1.7 times higher than the NPs with no TPGS-FOL component after 30min incubation. The MCF-7 cell viability was found decreased significantly from 50.8% for the drug-loaded NPs of no TPGS-FOL to 8.2% for those of 50% TPGS-FOL after incubation at 100microug concentration at 37 degrees C. The latter NPs also exhibited much lower IC(50) value than the DOX after 24h incubation, i.e., 19.4 vs. 43.7micror MCF-7 cells and 3.3 vs. >100micror C6 cells.
采用溶剂萃取/蒸发法制备了负载阿霉素的维生素E TPGS-叶酸（TPGS-FOL）共轭物纳米颗粒（NPs）和阿霉素-聚（丙交酯-共-乙交酯）-维生素E TPGS（DOX-PLGA-TPGS）共轭物纳米颗粒，用于富含叶酸受体肿瘤的靶向化疗。X射线光电子能谱表明叶酸分布在纳米颗粒表面，而药物分子包裹在纳米颗粒基质中。发现纳米颗粒直径约为350nm，体外药物释放呈现双相模式。对荧光纳米颗粒的细胞摄取和纳米颗粒中所配制药物的细胞活力进行了定量研究，发现其取决于靶向TPGS-FOL共轭物的含量。孵育30分钟后，50% TPGS-FOL的纳米颗粒被MCF-7细胞摄取的量比不含TPGS-FOL成分的纳米颗粒高1.5倍，被C6细胞摄取的量高1.7倍。在37℃下以100μg浓度孵育后，发现MCF-7细胞活力从不含TPGS-FOL的载药纳米颗粒的50.8%显著降低至50% TPGS-FOL的载药纳米颗粒的8.2%。孵育24小时后，后一种纳米颗粒的IC50值也比阿霉素低得多，即MCF-7细胞为19.4对43.7μg，C6细胞为3.3对>100μg。
