Novel Drug Delivery Laboratory, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Int J Nanomedicine. 2011;6:1903-12. doi: 10.2147/IJN.S23211. Epub 2011 Sep 8.
The objective of this study was to develop pegylated poly lactide-co-glycolide acid (PLGA) immunonanocarriers for targeting delivery of docetaxel to human breast cancer cells.
The polyethylene glycol (PEG) groups on the surface of the PLGA nanoparticles were functionalized using maleimide groups. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) antigens of cancer cells, used as the targeting moiety, was attached to the maleimide groups on the surface of pegylated PLGA nanoparticles. Nanoparticles prepared by a nanoprecipitation method were characterized for their size, size distribution, surface charge, surface morphology, drug-loading, and in vitro drug release profile.
The average size of the trastuzumab-decorated nanoparticles was 254 ± 16.4 nm and their zeta potential was -11.5 ± 1.4 mV. The average size of the nontargeted PLGA nanoparticles was 183 ± 22 nm and their zeta potential was -2.6 ± 0.34 mV. The cellular uptake of nanoparticles was studied using both HER2-positive (SKBR3 and BT-474) and HER2-negative (Calu-6) cell lines.
The cytotoxicity of the immunonanocarriers against HER2-positive cell lines was significantly higher than that of nontargeted PLGA nanoparticles and free docetaxel.
本研究旨在开发聚乙二醇化聚乳酸-共-乙醇酸（PLGA）免疫纳米载体，以实现多西紫杉醇对人乳腺癌细胞的靶向递药。
PLGA 纳米粒子表面的聚乙二醇（PEG）基团通过马来酰亚胺基团进行功能化。曲妥珠单抗，一种针对癌细胞表皮生长因子受体 2（HER2）抗原的单克隆抗体，用作靶向部分，被连接到聚乙二醇化 PLGA 纳米粒子表面的马来酰亚胺基团上。通过纳米沉淀法制备的纳米粒子，对其粒径、粒径分布、表面电荷、表面形态、载药量和体外药物释放曲线进行了表征。
曲妥珠单抗修饰的纳米粒子的平均粒径为 254±16.4nm，其 zeta 电位为-11.5±1.4mV。非靶向 PLGA 纳米粒子的平均粒径为 183±22nm，其 zeta 电位为-2.6±0.34mV。使用 HER2 阳性（SKBR3 和 BT-474）和 HER2 阴性（Calu-6）细胞系研究了纳米粒子的细胞摄取。
免疫纳米载体对 HER2 阳性细胞系的细胞毒性明显高于非靶向 PLGA 纳米粒子和游离多西紫杉醇。
