纳米磁小体氟尿嘧啶微球靶向治疗肝癌的实验研究

Experimental study on treatment of liver cancer by magnetic nanoparticle targeting

目的评价纳米磁性氟尿嘧啶微球治疗肝癌的靶向效应。方法肝癌裸鼠模型32只，随机分成4组：实验组，采用自制的0．03T强度的磁性支架丝，在肿瘤内部建立磁场，尾静脉注射氟尿嘧啶纳米磁小体；生理盐水对照组，无磁场和药物应用；单纯内磁场组，建立0．03T肿瘤局部内磁场，无药物治疗；单纯氟尿嘧啶治疗组，尾静脉注射氟尿嘧啶注射液，无磁场应用。各组于治疗前及连续5d治疗完成后第1，4，7，10，13天各用游标卡尺测量肿瘤大小。电镜观察肿瘤组织病理变化。结果实验组肿瘤抑制率64．0％，与其他三组的肿瘤体积有显著性差异（P〈0．05），该组肿瘤组织镜下显示大量细胞凋亡。结论纳米磁性氟尿嘧啶微球在内磁场的作用下有明显的靶向治疗效应。

Objective To investigate the targeting effect of magnetic microsphere containing 5-fluorouracil in treatment of liver cancer. Methods Thirty-two nude mice with liver cancer model were randomized into 4 groups. In group A, the internal magnetic field was built by magnetic stent wires inserted into tumor tissue to receive magnetic microsphere containing 5-fluorouracil administered via tail vein injection at 250 mg/kg for 5 d. In group B, the mice received placebo （sodium chloride）. The mice in group C received pure magnetic stent without use of magnetic nanoparticles. The mice in group D received pure 5-fluorouraeil administration via tail vein injection at 25 mg/kg for 5 d. The tumor was measured on the first day of treatment and 1, 4, 7, 10 and 13 d after the treatment. Tumor tissues were observed with transmission electron microscopy after the observation period. Results Repeat measure analysis of variance showed that group A had a tumor control rate of 64.0 %, which was significantly higher than that in other 3 groups （P〈0.05）. Meanwhile, more apoptotic tumor cells could be seen in group A. Conclusion Magnetic nanoparticles containing 5-fluorouracil can inhibit the growth of liver cancer and show significant effect of magnetic targeting after building magnetic field in side the tumor.