5-FU-CN的特性及其抗肿瘤效果评价

Characteristics and anti-tumor effect of 5-fluorouracil-chitosan nanoparticles

目的以壳聚糖作为抗肿瘤药物载体制备5-氟尿嘧啶-壳聚糖纳米粒（5-FU-CN），检测其形态及缓释特性，并考察其体外的抗肿瘤效果。方法利用离子凝胶法制备空白壳聚糖纳米粒（CN）及5-FU-CN；用透射电镜观察CN和5-FU-CN的形态及大小；通过紫外分光光度法测定该药物的体外释放曲线；采用四唑盐比色试验（MTT）法检测CN对卵巢癌细胞A2780的生长抑制作用，比较裸药5-Fu与5-Fu-CN的抗肿瘤效果；流式细胞仪观察CN、裸药5-Fu、5-Fu-CN对卵巢癌细胞A2780细胞周期的影响。结果用透射电镜观察到的CN为规则的圆形，粒径大小在30～60nm范围内，包埋药物后体积增大：体外缓释曲线显示5-Fu-cN具有良好的缓释特性；MTT试验表明CN对A2780细胞具有生长抑制作用，且具有浓度和时间依赖性，320μg／mLCN作用于细胞48小时细胞的生长抑制率可达26％作用。5-FU经壳聚糖纳米粒包埋后形成5-FU-CN，对细胞的杀伤作用随时间增长而增加；CN能够明显增加卵巢肿瘤细胞A2780在G，期的比例，5-Fu经壳聚糖纳米粒包埋后，对卵巢肿瘤细胞A2780在S期的抑制作用明显减弱，对G1期的抑制作用明显加强。结论CN具有-定抗肿瘤作用，5-FU经壳聚糖纳米粒包埋后形成5-FU-CN，能达到药物缓慢释放的效应，在药物作用晚期对肿瘤细胞的生长抑制作用加强，与此同时增加了对肿瘤细胞G1期的抑制作用。

Objective To prepare 5-fluorouracil-chitosan nanoparticles （5-FU-CN） by using chitosan （CTS） as a drug carrier and detect its morphous and slow release character, and then to evaluate the anti-tumor effect of 5-FU-CN in-vitro. Methods Blank chitosan nanoparticles （CN） and 5-FU-CN were prepared by ionotropic gelation method. The morphology of CN and 5-FU-CN was observed by transmission electron microscopy, and in-vitro release curve was measured by Uv spectrophotometer. Growth inhibiting of CN on ovarian cancer cell A2780 was tested by MT＇F and the anti-tumor effect of naked 5-FU and 5-FU-CN was compared. FCM was used to observe the influence of CN, naked 5-FU and 5-FU-CN on cell cycle of ovarian cancer cell A2780. Results CN were found to be round under transmission electron microscope with diameter of 30-60nm, and they enlarged after embedding drug. Release study of 5-FU-CN in-vitro indicated that they had a diffusion controlled release feature. CN inhibited the growth of A2780 in does- and time-dependent manner. After culture for 48h, the inhibition rate of A2780 cells treated with 320μg/mL was about 26%. Embedded by CN, 5-FU changed into 5-FU-CN and their killing effects strengthened with time going on. CN could increase the proportion of A2780 in G1 phase remarkably. Inhibitive effect of 5-FU-CN on A2780 decreased obviously in S phase, but increased significantly in G1 phase. Conclusion CN have certain function of tumor resistance. When 5-FU is embedded with CN and changes into 5-FU-CN, slow release can be controlled. In late period of drug action the inhibitive effect on growth of tumor cell strengthens, meanwhile the inhibitive effect on tumor cell in G1 phase, is increased.