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

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

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/m L vs.(2.5±0.39)μg/m L],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。

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.