【摘要】 目的研究甘草酸表面修饰壳聚糖纳米粒对肝实质细胞的靶向结合作用。方法通过流式细胞术研究大鼠肝实质细胞对罗丹明B异硫氰酸标记壳聚糖纳米粒(RBITC-CS-NPs)和甘草酸表面修饰壳聚糖纳米粒(RBITC-CS-NPs-GL)的结合及摄取作用。结果RBITC-CS-NPs和RBITC-CS-NPs-GL与肝实质细胞结合后,与空白对照组对比,细胞体积(FS)增大、胞浆内的颗粒(SS)增多;RBITC-CS-NPs-GL结合组荧光强度表达高于RBITC-CS-NPs结合组。以不同浓度的RBITC-CS-NPs和RBITC-CS-NPs-GL分别处理肝实质细胞,在25μg·mL-1和50μg·mL-1浓度下,细胞对RBITC-CS-NPs-GL的转染率显著高于RBITC-CS-NPs组(P<0.01),在高浓度(300g·mL-1、500μg·mL-1)下,细胞对纳米粒的摄取呈饱和状态,转染效率达90%以上;与细胞结合的起始阶段(1h内),RBITC-CS-NPs-GL与肝实质细胞通过甘草酸介导的主动靶向结合作用明显。结论肝实质细胞表面存在甘草酸的结合位点,以甘草酸修饰壳聚糖纳米粒可通过甘草酸介导的方式促进含药载体的肝靶向输送。更多还原

【Abstract】 Objective To study the target binding of chitosan nanoparticles with glycyrrhizin surface modification to hepatic parenchymal cells in vitro. Methods Flow cytometry was used to study the binding and intake capability of hepatocytic cells to chitosan nanoparticles labeled with rhodamine B isosulfocyanic acid (RBITC-CS-NPs) or to chitosan nanoparticles modified with glycyrrhizin (RBITC-CS-NPs-GL) on the surface. Results Compared with the control group,the size of the cells got enlarged and the number of granules in cytoplasm increased after the combination of hepatic parenchymal cells with RBITC-CS-NPs or RBITC-CS-NPs-GL.The fluorescence intensity expression in the cells combined with RBITC-CS-NPs-GL was higher than that in the cells combined with RBITC-CS-NPs.After being exposed to different concentrations of RBITC-CS-NPs or RBITGCS-NPs-GL,the transfection rate of hepatic parenchymal cells to RBITC-CS-NPs-GL was markedly higher than that to RBITC-CS-NPs especially at the concentration of 25μg·mL-1and 50μg·mL-1(P<0.01).The intake of the nanoparticles by the cells was saturated at 300 g·mL-1 and 500μg·mL-1,and the transfection rate was over 90%. At the initial phase of the combination of RBITC-CS-NPs-GL with the cells(within one hour),their active targeting binding mediated by glycyrrhizin was obvious. Conclusion There is a combination site of glycyrrhizin on the surface of hepatic parenchymal cells,and chitosan nanoparticles with glycyrrhizin surface modification may enhance the hepatic-targeting transportation of the drug-containing carrier through the mediation of glycyrrhizin.更多还原