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
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.