基础研究(Basic Research)

载5- 氟脲嘧啶聚己内酯纳米粒子对人胆管癌细胞的体外杀伤作用

Published at: 2015年第24卷第2期

李永盛 1 , 贺思佳 2 , 江翰 1 , 边睿 1 , 王硕 1 , 郝袁 1 , 王雪峰 1 , 刘颖斌 1 , 徐雷鸣 2 , 施伟斌 1
1 上海交通大学医学院附属新华医院普通外科/ 胆道研究所,上海 200092
2 上海交通大学医学院附属新华医院消化内科,上海 200092
通讯作者 伟斌 施 Email: weibindr@yahoo.cn
DOI: 10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2015.02.010
基金:
上海市科学技术委员会纳米科技专项课题资助项目 11nm0503700

摘要

目的:探讨聚己内酯载5- 氟尿嘧啶(5-FU)纳米粒子对人胆管癌细胞株的体外杀伤作用、安全性及机制。方法:超声乳化法制备载5-FU 聚己内酯纳米粒子(5-FU-PCL-NP),观察空载纳米粒子的体外溶血及5-FU-PCL-NP 的体外药物释放情况,检测5-FU-PLA-NP 对人胆管癌细胞株Hccc-9810 增殖抑制及凋亡诱导作用。结果:5-FU-PCL-NP 成功合成,其载药率为15.1%,包封率为41.9%,溶血试验阴性,5-FU-PCL-NP体外释放5-FU 缓慢,其72 h 释放率为62.9%。与单纯5-FU 比较,5-FU-PCL-NP 对Hccc-9810 细胞的增殖抑制作用明显增强,IC50 明显降低[(1.32±0.12)μg/mL vs.(2.5±0.39)μg/mL],促Hccc-9810细胞凋亡作用明显增强(均P<0.05)。空载纳米粒对Hccc-9810 细胞凋亡无明显影响(P>0.05)。结论:载5-FU 聚己内酯纳米粒子5-FU-PCL-NP 具有良好的药物缓释效应,可延长5-FU 的作用时间窗,对胆管癌细胞有较好的体外杀伤作用,且生物安全性好。


Killing effect of 5-fluorouracil loaded polycaprolactone nanoparticles on human cholangiocarcinoma cells in vitro

Abstract

Objective: To investigate the killing effect of 5-fluorouracil (5-FU) loaded polycaprolactone nanoparticles on human cholangiocarcinoma cells in vitro, and its safety and mechanism. Methods: The 5-FU loaded polycaprolactone nanoparticles (5-FU-PCL-NPs) were prepared by ultrasonic emulsification. In vitro hemolysis of the empty nanoparticles and drug release of 5-FU-PCL-NPs was observed, and the inhibition of proliferation and induction of apoptosis of 5-FU-PCL-NPs in human cholangiocarcinoma Hccc-9810 cells were determined. Results: The 5-FU-PCL-NPs were successfully synthesized, with drug loading rate of 15.1% and encapsulation efficiency of 41.9%. The empty nanoparticles showed a negative result in hemolysis test. 5-FU-PCL-NPs exhibited a sustained 5-FU release and the 72-h release rate was 62.9%. Compared with pure 5-FU, 5-FU-PCL-NPs had a significantly increased inhibitory effect on proliferation in Hccc-9810 cells, significantly decreased IC50 value [(1.32±0.12) μg/mL vs. (2.5±0.39) μg/mL], and significantly enhanced effect on apoptosis in Hccc-9810 cells (all P<0.05). The empty nanoparticles exerted no obvious effect on apoptosis in Hccc-9810 cells (P>0.05). Conclusion: The 5-FU loaded polycaprolactone nanoparticles (5-FU-PCL-NPs) possess a sustainedrelease property that prolongs the suppressive effect of 5-FU, and have enhanced killing effect on human cholangiocarcinoma cells in vitro, with a satisfactory biological safety profile.


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引用

引用本文: 永盛 李, 思佳 贺, 翰 江, 睿 边, 硕 王, 袁 郝, 雪峰 王, 颖斌 刘, 雷鸣 徐, 伟斌 施. 载5- 氟脲嘧啶聚己内酯纳米粒子对人胆管癌细胞的体外杀伤作用[J]. 中国普通外科杂志, 2015, 24(2): 206-210.
Cite this article as: LI Yongsheng, HE Sijia, JIANG Han, BIAN Rui, WANG Shuo, HAO Yuan, WANG Xuefeng, LIU Yingbin, XU Leiming, SHI Weibin . Killing effect of 5-fluorouracil loaded polycaprolactone nanoparticles on human cholangiocarcinoma cells in vitro[J]. Chin J Gen Surg, 2015, 24(2): 206-210.