Luo Laibin, Tam Joseph, Maysinger Dusica, Eisenberg Adi
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, H3A 2K6, Canada.
Bioconjug Chem. 2002 Nov-Dec;13(6):1259-65. doi: 10.1021/bc025524y.
Poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) block copolymers self-assemble into micelles in aqueous solution. We have examined whether these micelles can internalize into P19 cells in vitro. Fluorescently labeled PEO(45)-b-PCL(23) block copolymer was prepared by conjugating a tetramethylrhodamine molecule to the end of the hydrophobic PCL block. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies yielded 24 +/- 2 and 25 +/- 2 nm, respectively, for the diameters of the micelles. The studies also showed that chemical labeling did not effect the morphology or size. When the rhodamine-labeled PEO(45)-b-PCL(23) block copolymer micelles were tested in vitro, time-, concentration-, and pH-dependence of the internalization process suggested that internalization proceeded by endocytosis. The results from these studies provide the first direct evidence for the internalization of PEO(45)-b-PCL(23) micelles. Future studies will utilize multiple labeling of these micelles, allowing questions to be addressed related to the fate of internalized micelles as drug carriers, the destination of the incorporated drugs or fluorescent probes released from micelles, and the identification of the subcellular localization of the whole drug-carrier system within cells, both in vitro and in vivo.
聚环氧乙烷 -b-聚己内酯（PEO-b-PCL）嵌段共聚物在水溶液中自组装形成胶束。我们已经研究了这些胶束在体外是否能够内化进入P19细胞。通过将四甲基罗丹明分子连接到疏水性PCL嵌段的末端，制备了荧光标记的PEO(45)-b-PCL(23)嵌段共聚物。动态光散射（DLS）和透射电子显微镜（TEM）研究得出胶束直径分别为24±2和25±2纳米。研究还表明化学标记不影响形态或尺寸。当对罗丹明标记的PEO(45)-b-PCL(23)嵌段共聚物胶束进行体外测试时，内化过程的时间、浓度和pH依赖性表明内化是通过内吞作用进行的。这些研究结果为PEO(45)-b-PCL(23)胶束的内化提供了首个直接证据。未来的研究将对这些胶束进行多重标记，从而能够解决与作为药物载体的内化胶束的命运、从胶束中释放的掺入药物或荧光探针的去向以及在体外和体内整个药物载体系统在细胞内的亚细胞定位鉴定相关的问题。
