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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 study the killing effect of glycyrrhizin-modified doxorubicin-loaded chitosan nanoparticles on human hepatoma cell line SMMC-7721. Methods: MTT assay was used to study the inhibitory effect of drug-loaded nanoparticles on the proliferation of tumor cells. The intracellular distribution of the nanoparticles and the morphological changes of the tumor cells before and after treatment were observed by laser confocal microscopy. The drug-loaded nanoparticles were studied by TUNEL staining Tumor cell apoptosis. RESULTS: Glycyrrhizin-modified doxorubicin-loaded chitosan nanoparticles enhanced the inhibitory effect on SMMC-7721 cells by 6.36-fold (compared with free drug), while the unmodified doxorubicin-loaded chitosan nanoparticles inhibited tumor cell killing No significant increase. Confocal laser scanning microscope can be seen glycyrrhizic acid-mediated nanoparticles to promote doxorubicin to the nucleus distribution, thereby enhancing the anti-tumor effect of doxorubicin. TUNEL staining proved glycyrrhizic acid-mediated nanoparticles can promote the doxorubicin on the nucleus DNA fragmentation and nuclear disintegration, increased doxorubicin on tumor cell apoptosis. CONCLUSION: Glycyrrhizin surface-modified doxorubicin chitosan nanoparticles can be used as a potential active carrier in the treatment of hepatocellular liver disease. Its in vivo pharmacodynamic evaluation deserves further study.