Fadaeian Ghazal, Shojaosadati Seyed Abbas, Kouchakzadeh Hasan, Shokri Fazel, Soleimani Masoud
Biotechnology Group, Chemical Engineering Faculty , Tarbiat Modares University, Tehran, Iran.
Department of Immunology, School of Public Health, Tehran University of Medical Science, Tehran, Iran. ; Monoclonal Antibody Research Center, Avicenna Research Institute, Tehran, Iran.
Iran J Pharm Res. 2015 Spring;14(2):395-405.
Herein, 1F2, an anti-HER2 monoclonal antibody (mAb), was covalently coupled to the surface of 5-Fluorouracil (5-FU) loaded bovine serum albumin (BSA) nanoparticles. Concerning two different crosslinkers for conjugation of 1F2, Maleimide-poly (ethylene glycol)-Succinimidyl carbonate (Mal-PEG5000-NHS) was selected due to its higher conjugation efficiency (23 ± 4%) obtained in comparison to N-succinimidyl 3-(2-Pyridyl Dithio) Propionate (SPDP) (8 ± 2%). A slight increase in the average particle size with a negligible prolongation of the 5-FU release was observed after 1F2 coupling. The 1F2-coupled 5-FU-loaded BSA nanoparticles interacted with nearly all HER2 receptors available on the surface of HER2-positive SKBR3 cells. No cellular uptake was observed for HER2-negative MCF7 cells. Physicochemical and biological properties of the mAb-modified nanoparticles did not significantly alter after three months of storage at room temperature. The in-vitro cytotoxicity evaluation by MTT assay, demonstrated lower SKBR3 viability (50.7 ± 9 %) after 5 hours contact with 1F2-coupled 5-FU-loaded BSA nanoparticles in comparison with the other control systems due to their cell attachment and internalization after washing. In addition, no significant toxicity was observed on MCF7 cells. This novel system can efficiently be employed for targeted delivery of 5-FU to HER2-positive cancerous cells.
在此，抗HER2单克隆抗体（mAb）1F2共价偶联至负载5-氟尿嘧啶（5-FU）的牛血清白蛋白（BSA）纳米颗粒表面。关于用于1F2偶联的两种不同交联剂，由于与N-琥珀酰亚胺基3-（2-吡啶基二硫代）丙酸酯（SPDP）相比，其获得了更高的偶联效率（23±4%），因此选择了马来酰亚胺-聚（乙二醇）-琥珀酰亚胺基碳酸酯（Mal-PEG5000-NHS）（8±2%）。在1F2偶联后，观察到平均粒径略有增加，而5-FU释放的延长可忽略不计。1F2偶联的负载5-FU的BSA纳米颗粒与HER2阳性SKBR3细胞表面几乎所有可用的HER2受体相互作用。未观察到HER2阴性MCF7细胞的细胞摄取。在室温下储存三个月后，mAb修饰的纳米颗粒的物理化学和生物学性质没有显著改变。通过MTT试验进行的体外细胞毒性评估表明，与其他对照系统相比，在与1F2偶联的负载5-FU的BSA纳米颗粒接触5小时后，SKBR3细胞活力较低（50.7±9%），这是由于洗涤后它们的细胞附着和内化。此外，未观察到对MCF7细胞有明显毒性。这种新型系统可有效地用于将5-FU靶向递送至HER2阳性癌细胞。
