氟尿嘧啶-壳寡糖/硒纳米微球的制备及抑制肿瘤细胞生长活性

为研究抗肿瘤药物与辅药负载于同一药物载体的作用效果, 首先以壳寡糖和广谱抗肿瘤药物5-氟尿嘧啶(5-Fu)为原料通过化学键合合成氟尿嘧啶-壳寡糖前体, 然后以其为模板通过溶胶-凝胶法制备了同时负载氟尿嘧啶和硒纳米颗粒的壳寡糖微球. 采用透射电子显微镜(TEM)、 Zeta电位仪和红外光谱(IR)对制备的微球进行了表征, 结果表明, 微球粒径为433 nm, 硒纳米颗粒包裹在微球内; 对微球包裹药物进行检测发现, 5-Fu装载率为(8.2±0.3)%, 硒装载率为(7.96±0.34)%; 体外缓释检测和细胞实验结果证实, 微球能够缓慢释放2种药物, 其缓释作用能很好地抑制肝癌细胞SMMC-7721的生长.

Preparation of Micro-spheres Co-carried Anti-tumor Drug and Sensitizer(5-Fu-COS/SeNP) and Their Inhibiting Tumorous Cellular Growths Activity†

5-Fu-COS/SeNP micro-spheres were prepared in two steps to study the antitumor drug load and auxiliary same effects as the drug carrier. First, the Fu-COS prodrug was synthesized with the broad-spectrum anti-tumor drug 5-fluorouracil(5-Fu) and chito-oligosaccharides(COS), then, Fu-COS was used as temples while 5-Fu-COS/SeNP was prepared by sol-gel method. 5-Fu-COS/SeNP was characterized by TEM, Zeta-sizer and IR, and its anti-tumor activity was detected by MTT method. The results showed that 5-Fu and Se were completely carried in 5-Fu-COS/SeNP, the size of 5-Fu-COS/SeNP was 433 nm, the drug-loading rate of 5-Fu and Se were (8.2±0.3)% and (7.96±0.34)%, respectively, and 5-Fu and nanose released slowly and had well inhibiting tumorous cellular growths activity. As time increases, release rate of the drug by Fu-COS/SeNP increased and the inhibition of cell enhanced. After 24 h, inhibition rate had exceeded the sum of 5-Fu and SeNP. After 48 h, the inhibition rate of Fu-COS/SeNP was less than the sum of the inhibition rate of 5-Fu and SeNP, but higher than that of 5-Fu or SeNP. These results indicated that the spheres have high drug loading efficiency and good drug release properties. This novel method to produce micro-spheres could expand the development of drug release research.