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目的该研究旨在探讨叶酸修饰四代聚酰胺-胺型枝状聚合物纳米粒对肝癌Hep G2靶向效果,为构建新型的靶向肝癌的纳米递送系统提供实验数据。方法 MTT法确定Hep G2细胞摄取PAMAM NPs和PAMAM-叶酸NPs适当的浓度;通过激光共聚焦和荧光显微镜定性观察Hep G2对罗丹明B标记的PAMAM NPs和PAMAM-叶酸NPs的摄取;并采用流式细胞计数仪定量研究Hep G2细胞对两者的摄取差别;尾静脉注射荷Hep G2瘤裸鼠研究两者体内分布情况。结果 PAMAM NPs和PAMAM-叶酸NPs的浓度在0.2 mg/m L时细胞存活率较高且对Hep G2细胞的毒性较小。激光共聚焦断层扫描显示Hep G2细胞可以较好地摄取PAMAM-叶酸NPs,同时流式细胞仪定量显示PAMAM-叶酸NPs在Hep G2细胞的分布较PAMAM NPs高40%(P<0.05)。PAMAM NPs和PAMAM-FANPs在移植瘤中的分布明显多于其他脏器,并且随时间的延长PAMAM-FA NPs体现了更好的靶向效果。结论体外与体内实验证明FA修饰的PAMAM NPs对肝癌细胞Hep G2有很好的靶向效果,可为肝癌的靶向治疗提供较好的药物载体。
OBJECTIVE: To investigate the effect of folate-modified fourth-generation polyamide-amine dendrimer nanoparticles on Hep G2 hepatocellular carcinoma cells and to provide experimental data for the construction of a novel nano-delivery system targeting liver cancer. Methods The appropriate concentration of PAMAM NPs and PAMAM-folate NPs in Hep G2 cells was determined by MTT assay. The uptake of rhodamine B-labeled PAMAM NPs and PAMAM-folate NPs by Hep G2 was observed by laser scanning confocal microscope and fluorescence microscope. Cell counter quantitative study of Hep G2 cells uptake of the difference between the two; tail vein injection of Hep G2 tumor-bearing nude mice in vivo distribution of the two. Results The cell viability of PAMAM NPs and PAMAM-folic acid NPs was higher at 0.2 mg / mL and less toxic to Hep G2 cells. Confocal laser scanning confocal microscopy showed that PAMAM-NPs could be uptake by Hep G2 cells. Flow cytometry showed that the distribution of PAMAM-NPs in Hep G2 cells was 40% higher than PAMAM NPs (P <0.05). The distribution of PAMAM NPs and PAMAM-FANPs in xenograft tumors was significantly more than that in other organs, and PAMAM-FA NPs exhibited better targeting effects over time. Conclusion In vitro and in vivo experiments demonstrated that FA-modified PAMAM NPs have a good targeting effect on Hep G2 cells and provide a good drug carrier for the targeted therapy of HCC.