甘草次酸修饰壳聚糖5-氟尿嘧啶对肝癌的抑制作用

目的观察甘草次酸修饰壳聚糖5-氟尿嘧啶纳米粒的体内外肝癌的靶向性及其对肝癌细胞的抑制作用。方法将甘草次酸（GA）和壳聚糖（CTS）合成甘草次酸修饰的壳聚糖纳米材料甘草次酸修饰的壳聚糖（GA-CTS），并与5-氟尿嘧啶（5-Fu）合成GA-CTS／5-Fu纳米粒，通过共聚焦实验观察该纳米材料的肝癌靶向性，在原位肝癌模型中的药物分布，及其对肝癌细胞的体外抑制作用。结果GA和CTS成功合成GA-CTS，并通过红外光谱和核磁共振氢谱的验证。将GA-CTS与5-Fu制备成GA-CTS／5-Fu纳米粒。其粒径为193．7nm，栽药量为1．56％，多分散指数为0．003，并具有缓释的特性，能达到快速释放、稳步释放和缓慢释放三个阶段。GA-CTS／5-Fu纳米粒在体内分布表明，肝脏的5-Fu浓度最高，可见纳米粒具有明显的肝脏靶向性。激光共聚焦显微镜分析亦发现GA-CTS／5-Fu纳米粒具有明显的肝癌靶向性。体外对肿瘤细胞的杀伤作用具有时间和剂量依赖关系，对肝癌细胞有效作用时间明显比5-Fu延长。同时发现GA-CTS纳米粒具有明显对肝癌耐药细胞株抑制作用。结论GA-CTS／5-Fu纳米粒具有缓释作用，并且具有肝癌靶向性和明显的肿瘤抑制作用。

The inhibition of synthesis of glycyrrhetinic acid-modified chitosan 5 - fiuorouracil nanoparticles on liver cancer

Objective It is to observe the targeting of glycyrrhetinic acid-modified chitosan 5 - fluorouracil（5 - Fu） nanoparticles （ GA - CTS/5 - Fu） to liver cancer in vitro and their inhibition on liver cancer cells in vivo. Methods The glycyrrhetinic acid-modified chitosan nano-materials （GA - CTS） were synthesized gIycyrrhetinic acid （GA） combined with chitosan （CTS） , GA - CTS/5 - Fu nanoparticles were GA - CTS combined with 5 - Fu. The nanomaterials of targeting liver cancer were observed experimentally by confocal, the drug distribution of 5 - Fu were performed via liver cancer model, and their inhibitory effect on liver cancer cells in vitro. Results GA - CTS was successful synthesized with GA and GTS, which was confirmed by IR spectra and 1H - NMR. Combining GA - CTS and 5 - Fu, we obtained GA - CTS/5 - Fu nanoparticle, with particle size of 193.7 nm, drug loading of 1.56% and polydispersity index of 0. 003. GA - CTS/5 - Fu nanoparticle was a sustained release system showing three phases as quick, steady and slow release. The nanoparticle was observed to accumulate in liver. In vitro data demonstrated it had dose and time-dependent anti-cancer effect, and increased effective time against hepatic cancer cells was observed for GA - CTS/5 - Fu compared with 5 - Fu. Conclusion The GA - CTS/5 - Fu nanopartieles have sustained release effect, targeted therapy, and obvious inhibition of liver cancer.