Zhang Xiaoran, Li Jinxiu, Yan Meixing
a Ji'nan Central Hospital Affiliated to Shandong University , Ji'nan , People's Republic of China ;
b Department of Pharmacy , Binzhou People ' s Hospital , Binzhou , People's Republic of China ;
Drug Dev Ind Pharm. 2016 Oct;42(10):1590-9. doi: 10.3109/03639045.2016.1160103. Epub 2016 Mar 17.
Targeted hepatocellular carcinoma (HCC) therapy was carried out to improve the efficacy of liver cancers. The aim of this study was to develop transferrin (Tf) modified, self-assembled polymeric nanoparticles for co-delivery doxorubicin (DOX) and cisplatin (DDP), to achieve combination tumor therapy.
Tf modified polyethylene glycol (PEG) containing DOX prodrug (Tf-PEG-DOX) was synthesized. DDP containing poly(lactic-co-glycolic) acid (PLGA) materials (PLGA-DDP) were prepared. Tf modified DOX and DDP loaded PLGA nanoparticles (Tf-DOX/DDP NPs) were prepared by using nanoprecipitation method. The particles sizes, zeta potentials, drug loading effects were characterized. The cytotoxicity of the NPs was evaluated in human hepatoma carcinoma cell lines (HepG2 cells), and in vivo anti-tumor was observed in mice bearing human HepG2 cells model.
Tf-DOX/DDP NPs displayed higher cytotoxicity and enhanced antitumor activity both in vitro and in vivo over their non-modified and single drug loaded counterparts.
Tf-DOX/DDP NPs can achieve outstanding anti-tumor activity due to the combination effect of two drugs and the active targeting ability of Tf ligands. The self-assembled polymeric nanomedicine could act as an efficient therapy method for HCC treatment.
开展靶向肝细胞癌(HCC)治疗以提高肝癌疗效。本研究的目的是开发转铁蛋白(Tf)修饰的自组装聚合物纳米颗粒,用于共递送阿霉素(DOX)和顺铂(DDP),以实现联合肿瘤治疗。
合成了含DOX前药的Tf修饰聚乙二醇(PEG)(Tf-PEG-DOX)。制备了含DDP的聚乳酸-羟基乙酸共聚物(PLGA)材料(PLGA-DDP)。采用纳米沉淀法制备了Tf修饰的载DOX和DDP的PLGA纳米颗粒(Tf-DOX/DDP NPs)。对颗粒大小、zeta电位、载药效果进行了表征。在人肝癌细胞系(HepG2细胞)中评估了纳米颗粒的细胞毒性,并在人HepG2细胞模型小鼠中观察了体内抗肿瘤效果。
与未修饰和单药负载的纳米颗粒相比,Tf-DOX/DDP NPs在体外和体内均表现出更高的细胞毒性和增强的抗肿瘤活性。
由于两种药物的联合作用以及Tf配体的主动靶向能力,Tf-DOX/DDP NPs可实现出色的抗肿瘤活性。这种自组装聚合物纳米药物可作为一种有效的HCC治疗方法。