Fe_3O_4纳米粒对热疗大鼠皮下肿瘤影响的研究

Therapy of Fe_3O_4 magnetic nanometer particle targeted hyperthermia on subcutaneous tumor model in rats

目的：研究Fe3O4磁性纳米粒靶向治疗大鼠Walker-256皮下肿瘤的作用。方法：建立大鼠皮下移植瘤模型,将Fe3O4纳米粒注入肿瘤后置入交变磁场中,分别治疗1（MTH1）、2（MTH2）和3（MTH3）次。观察肿瘤体积抑制率、生存期及病理变化。结果：肿瘤内温度在6~10 min内达到50~55℃,周围正常组织不升温。磁靶向治疗对MTH2和MTH3组肿瘤在2周内有明显的肿瘤体积抑制作用,肿瘤体积抑制率分别为（65.0±3.5）%和（71.6±4.2）%。与NS（生理盐水）组比较,MTH3和MTH2的平均生存期延长,差异有统计学意义,P值分别为0.003和0.002;MTH1和MN（注入磁性纳米粒而未治疗）组的平均生存期差异无统计学意义,P值分别为0.093和0.785。NS和MN组癌细胞密集,核仁明显,易见核分裂像;MTH1、MTH2和MTH3组常见瘤内大片坏死残留的无结构红染物质或空洞,部分胞核有固缩、碎裂及崩解。结论：磁介导的靶向治疗能抑制大鼠Walker-256皮下肿瘤增殖,可能为实体瘤的治疗提供一种手段。

OBJECTIVE：To investigate the therapeutic effect of Fe3O4 magnetic nanometer particle targeted hyperthermia on Walker-256 tumor model in rats.METHODS： After tumor model was established,Fe3O4 magnetic nanometer particles were injected into tumor tissues.Then,they were placed under an alternating magnetic field for hyperthermia（1,2 and 3 times respectively,named as MTH1,MTH2 and MTH3）.The volume inhibition ratio,survival time and pathologic changes were observed.RESULTS： Temperature in tumor tissues could reached to 50-55 ℃ within 6-10 minutes,however,temperature in normal tissues was unchanged.From the volume-time curve,it was obvious that magnetic nanometer paticle targeted hyperthermia inhibited the tumor proliferation within two weeks,and the ratio of volume inhibition in MTH2 and MTH3 was（65.0±3.5）% and（71.6±4.2）%.The mean survival time of MTH3 and MTH2 groups was longer than that of NS group,and there were statistical significance（P were 0.003 and 0.002）;However,there were no statistical significance between MTH1 and MN groups（P were 0.093 and 0.785）.The cancer cells of NS and MN groups were thick and fast,and nucleus split stage could be seen easily.In the hyperthermia groups,there were big necrosis areas and red-dyed remnant,or cavity,and some nucleus shrank,split and dissolved.CONCLUSIONS： Fe3O4 magnetic nanometer particle targeted hyperthermia can inhibit the proliferation of subcutaneous tumor model in rats.It may also be a therapeutic method for other solid tumors.