Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanothechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Pharm. 2015 Feb 1;479(1):241-51. doi: 10.1016/j.ijpharm.2014.12.035. Epub 2014 Dec 18.
Targeted delivery of anti-cancer agents exclusively to tumor cells introduces an attractive strategy because it increases the therapeutic index compared with untargeted drugs. Aptamer conjugated nanoparticles that can specifically bind to the proteins on a tumor cell surface are capable nanoscale delivery systems for enhancing cellular uptake of chemotherapeutic agents. The epithelial cell adhesion molecule (EpCAM) as a cancer stem cell marker emerges as a versatile target for aptamer-based cancer therapy due to its high expression level in various adenocarcinoma cell lines and its very low expression level in normal cells. We developed EpCAM-targeted PEG-PLGA nanopolymersomes by covalently coupling the EpCAM aptamer to the surface of nanopolymersomes loaded with the anticancer agent doxorubicin via pH gradient method. The results indicated that doxorubicin was entrapped in PEG-PLGA nanopolymersomes with encapsulation efficiency and loading content of 91.25±4.27% and 7.3±0.34%, respectively. Over a period of 5 days, up to 8% of the DOX was released through this system. The doxorubicin-loaded aptamer conjugated nanopolymersomes exhibited efficient cell uptake and internalization, and were significantly more cytotoxic (P<0.01) toward EpCAM-positive tumor cells (MCF-7) than non-targeted nanopolymersomes. Our data suggest that EpCAM-targeted nanopolymersomes will lead to an improved therapeutic index of doxorubicin to EpCAM positive cancer cells.
靶向递送至肿瘤细胞的抗癌药物专门介绍了一个有吸引力的策略，因为它增加了治疗指数相比未靶向药物。适体偶联的纳米粒子，能特异性结合肿瘤细胞表面的蛋白质，是能够增强化疗药物细胞摄取的纳米级递药系统。上皮细胞黏附分子（EpCAM）作为癌症干细胞标志物，由于其在各种腺癌细胞系中的高表达水平和在正常细胞中的低表达水平，成为基于适体的癌症治疗的多功能靶标。我们通过 pH 梯度法，将 EpCAM 适体共价偶联到载有抗癌药物阿霉素的纳米聚合物囊泡表面，制备了 EpCAM 靶向的 PEG-PLGA 纳米聚合物囊泡。结果表明，阿霉素被包封在 PEG-PLGA 纳米聚合物囊泡中，包封效率和载药量分别为 91.25±4.27%和 7.3±0.34%。在 5 天的时间内，通过该系统释放了高达 8%的 DOX。载阿霉素的适体偶联纳米聚合物囊泡表现出高效的细胞摄取和内化作用，并且对 EpCAM 阳性肿瘤细胞（MCF-7）的细胞毒性明显高于非靶向纳米聚合物囊泡（P<0.01）。我们的数据表明，EpCAM 靶向纳米聚合物囊泡将导致阿霉素对 EpCAM 阳性癌细胞的治疗指数提高。
