载氟尿嘧啶聚乳酸碳纳米管复合材料对胃癌细胞株的体外杀伤效应

目的制备荷载氟尿嘧啶（5-Fu）的聚乳酸（PLLA）碳纳米管（CNT）复合材料（5-FU-PLLA-CNTs），并探讨其对人胃癌细胞株（MGC803和MNK45）的体外杀伤效应。方法以PLLA—CNTs为原料，采用超声乳化法荷载5．FU；通过扫描电子显微镜观察5-FU—PLLA—CNTs形态和结构；用紫外可见光光度仪测定不同时间5-FU．PLLA．CNTs的5-FU释放量及累计释放量，并绘制体外释放曲线；设计实验组（不同浓度的5-Fu—PuA—CNTs）及阳性（相应浓度的5-FU）和阴性对照组（不加任何药物），用CCK8法检测不同浓度的5-Fu．PLLA-CNTs对MGC803和MNK45的增殖抑制作用；流式细胞术检测5-FU—PuIA—CNTs作用前后细胞凋亡的变化。结果成功制备5-FU．PLLA．CNTs药物深层薄膜，薄膜载药率为（4．54±0．43）％，包封率（21．56±2．36）％。体外释放实验显示，5-FU-PLLA-CNTs在24h内释放率为23．9％，呈缓慢上升趋势，至31d体外累计释放率达85．3％。CCK8实验显示，与对照组比较，5．Fu—PLLA．CNTs对两株胃癌细胞具有明显抑制作用（P〈0．01），随着药物浓度的增加，抑制作用增强；随着作用时间的延长，呈持续抑制状态。流式细胞仪显示，经1mg／孔5-Fu-PuJA。CNTs处理的实验组MGC803和MNK45细胞凋亡率与阴性对照组比较，差异具有统计学意义（均P〈0．05）；与阳性对照组比较，差异无统计学意义（均P〉0．05）。结论5-FU-PLLA-CNTs具有良好的药物缓释性能，对胃癌细胞株具有明显的杀伤和抑制增殖作用，其最佳浓度为1mg／孔。

Anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines in vitro

Objective To prepare cisPLLAtin-loaded polylactic acid/cnts, and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines （MGC803 and MNK45）. Methods 5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU- PLLA-CNTs was determined by scanning electron microscope （SEM）, and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs. Results Deep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was （4.54±0.43）%, entrapment rate was （21.56±2.36）%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a aslowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed, as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose- dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 rag/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group （P〈0.05）, while the difference was not significant as compared to positive control group （P〉0.05）. Conclusion The 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.