Enhanced cellular uptake of folic acid-conjugated PLGA-PEG nanoparticles loaded with vincristine sulfate in human breast cancer
Enhanced cellular uptake of folic acid-conjugated PLGA-PEG nanoparticles loaded with vincristine sulfate in human breast cancer
复制标题
增强载有硫酸长春新碱的叶酸缀合 PLGA-PEG 纳米颗粒在人乳腺癌中的细胞摄取
DOI：
10.3109/03639045.2011.575162
复制
发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Chen, Jianian;Li, Shaoshun;Zhang, Yi
本文的目的是评估叶酸修饰的长春新碱硫酸盐负载聚乳酸-羟基乙酸-聚乙二醇（PLGA-PEG）纳米颗粒（PLGA-PEG-叶酸NPs）的细胞摄取。采用水-油-水乳液溶剂蒸发法制备了plga - peg -叶酸NPs。考察了其粒径、表面形貌、包封率和释药行为。NPs表现出两相的药物释放，先是适度的初始爆发，然后是持续释放。MCF-7 （Michigan Cancer Foundation-7）人乳腺癌细胞对香豆素-6标记的NPs的内化量采用微孔板仪定量测定，荧光显微镜和共聚焦激光扫描显微镜对NPs进行定性分析。结果显示，与未经叶酸修饰的PLGA-mPEG NPs相比，plga - peg -叶酸NPs在叶酸受体过表达的MCF-7细胞中获得了显著更高的细胞摄取。由于细胞摄取增强，plga - peg -叶酸NPs表现出最高的细胞毒性。培养24 h后通过IC（50）判断，经表面修饰的NPs中配制的药物的治疗效果分别是PLGA-mPEG NPs和游离硫酸长春新碱NPs的1.52倍和3.91倍。
The aim of this paper is to evaluate the cellular uptake of vincristine sulfate-loaded poly(lactic-co-glycolic acid)polyethylene glycol (PLGA-PEG) nanoparticles with the folic acid modification (PLGA-PEG-folate NPs). PLGA-PEG-folate NPs were prepared using a water-oil-water emulsion solvent evaporation method. The particle size, surface morphology, drug encapsulation efficiency, and the drug release behavior were investigated. The NPs exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. Internalization of the NPs labeled with coumarin-6 by MCF-7 (Michigan Cancer Foundation-7) human breast cancer cells was quantitatively measured by microplate reader, and qualitatively analyzed by fluorescent microscopy and confocal laser scanning microscopy. The results showed PLGA-PEG-folate NPs achieved significantly higher cellular uptake in the folic acid receptor overexpressed MCF-7 cells, compared to PLGA-mPEG NPs without the folic acid modification. Due to the enhanced cellular uptake, PLGA-PEG-folate NPs displayed the highest cytotoxicity. Judged by IC(50) after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface modification could be 1.52 times, 3.91 times higher than that of PLGA-mPEG NPs and free vincristine sulfate, respectively.