半乳糖-羧化壳聚糖-十四酸纳米粒的制备及其肝靶向性

Preparation of liver-targeted galactose-carboxyl chitosan-myristic acid nanoparticles

目的:制备半乳糖-羧化壳聚糖-十四酸纳米粒(galactose carboxyl chitosan myristic acid nanoparticles,GCCMA),观察GCCMA纳米粒在肝癌细胞中的靶向性.方法:本实验组采用自组装法制备GCCMA纳米粒,优化制备条件,并经过本实验组鉴定稳定性及生物相容性,纳米粒经荧光标记后分别取不同浓度转染肝癌细胞及HT22海马神经细胞,对照组、HT22海马神经细胞组和肝癌细胞组,以及对照组、肝癌细胞-low组、肝癌细胞-mid组和肝癌细胞-high组(置入的GCCMA纳米粒浓度由低到高),分别于1、2和4h时间点测定在细胞摄取纳米粒情况.结果:相同浓度的GCCMA纳米粒,Huh7肝癌细胞摄取量显著高于HT22海马神经细胞,肝癌细胞摄取量在特定区间有剂量依赖性,较高浓度时摄取量较大,在1、2和4h时间点所测定的结果显示,4h时肝癌细胞的摄取量最大.结论:GCCMA纳米粒有肝靶向性,为肝脏肿瘤的靶向性基因治疗或化疗药物提供很好的药物载体及给药途径.

AIM：To prepare galactose-carboxyl chitosan-myristic acid （GCCMA） nanoparticles and to obverse their targeting of hepatoma carcinoma cells （HCCs）. METHODS：GCCMA nanoparticles were prepared by self-assembled technology, and their stability and biocompatibility were assessed. After fluorescent labeling, GCCMA nanoparticles of different concentrations were transfected into HCCs and HT22 hippocampal neurons. Non-transfected HCCs and HT22 hippocampal neurons were used as controls. Based on the concentrations of GCCMA nanoparticles, HCCs transfected with GCCMA nanoparticles were divided into low-, medium- and high-concentration groups. The cellular uptake of nanoparticles was determined at 1, 2 and 4 h after transfection. RESULTS：The cellular uptake of nanoparticles in the HCC group was much higher than that in the HT22 hippocampal neuron group. The uptake of nanoparticles in the HCC group was dose-dependent. The highest uptake of nanoparticles in the HCC group was observed at 4 hours after transfection. CONCLUSION：GCCMA nanoparticles show hepatic targeting and are therefore a potential drug-carrier or administration route for chemotherapy drugs or targeted gene therapy for hepatic tumors.