甘草酸修饰阿霉素壳聚糖纳米粒对人肝癌细胞系SMMC-7721的杀伤作用研究

Anti-tumor Activity of Adriamycin-loaded Chitosan Nanoparticles Surface-modified with Glycyrrhizin on Human Hepatoma Cell Line SMMC-7721

目的:研究甘草酸修饰阿霉素壳聚糖纳米粒对人肝癌细胞系SMMC-7721的杀伤作用。方法:采用MTT实验研究载药纳米粒对肿瘤细胞增殖的抑制效应,激光共聚焦显微镜观察纳米粒的胞内分布及处理肿瘤细胞实验前后的形态学变化,应用TUNEL染色技术研究载药纳米粒诱导肿瘤细胞凋亡的情况。结果:甘草酸修饰阿霉素壳聚糖纳米粒对SMMC-7721细胞生长的抑制效应增强了6.36倍(与游离药物比较),而未修饰阿霉素壳聚糖纳米粒对肿瘤细胞的杀伤作用未见显著提高。激光共聚焦显微镜下可见甘草酸介导的纳米粒促进阿霉素向细胞核分布,从而提高了阿霉素的抗肿瘤作用。TUNEL染色技术证明甘草酸介导的纳米粒可促进阿霉素对细胞核内DNA的断裂及细胞核的破碎分解,增加阿霉素对肿瘤细胞诱导凋亡的作用。结论:甘草酸表面修饰阿霉素壳聚糖纳米粒可作为潜在的治疗肝细胞性肝脏疾病药物的主动传输载体,其体内药效学评价值得进一步研究。

OBJECTIVE： To investigate the anti-tumor activity of adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin on human hepatoma cell line SMMC-7721. METHODS： Inhibition effect of drug-loaded nanoparticle on the proliferation of SMMC-7721 cells was determined with MTT method. Intra-cellular distribution of nanoparticles and morphological change of SMMC-7721 cells before and after treatment were observed by confocal laser scanning microscope （CLSM） and the apoptosis induced by adriamycin was measured by TUNEL assay. RESULTS： The inhibition effect of adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin on the proliferation of SMMC-7721 cells increased 6.36 times lower in comparison with free drugs. The inhibition effect of adriamycin-loaded chitosan nanoparticles had no obvious improvement. Nanoparticles surface-modified with glycyrrhizin promoted the distrubition of adriamycin in the nucleus, so as to promote the anti-tumor activity of adriamycin. TUNEL assay indicated that nanoparticles surface-modified with glycyrrhizin induce DNA fragmentation and nucleus breakdown to induce the apoptosis of SMMC-7721 cells. CONCLUSION： Adriamycin-loaded chitosan nanoparticles surface-modified with glycyrrhizin can used as potential active hepatocyte-targeted delivery carrier. Pharmacokinetic evaluation of it is worthy of further studing.