电磁场介导纳米铁粒磁性顺铂微球栓塞热化疗治疗兔VX_2肝癌的作用

Effects of embolization thermochemotherapy induced by an alternating electromagnetic field mediated nano-ferroferric oxide cis-diammine-dichloroplatium magnetic microspheres on rabbit VX_2 liver tumor

目的探讨用交变电磁场(E)介导纳米氧化铁粒磁性顺铂微球(nCDDPmm)靶向栓塞热化疗治疗肝癌的作用。方法制备移植性兔 VX_2肝癌模型,随机分5组经肝动脉插管灌注:(1)对照组,生理盐水+40 kHz、24kA/min 的 E30min;(2)nCDDPmm(铁30mg/kg,顺铂2mg/kg)+E 组;(3)纳米铁粒磁性微球(nmm,铁30mg/kg)+E 组;(4)nCDDPmm 组:(5)nmm 组。用光纤温度测量仪监测癌中心区、癌边缘区、正常肝组织和直肠的温度变化;观察治疗时和治疗后14d 肝癌体积的变化,肿瘤生长率,肝癌和肝组织的病理变化。结果 nCDDPmm+E 和 nmm+E 组的癌中心区(43.71℃,43.66℃)和癌边缘(40.21℃,40.63℃)的温度显著高于正常肝组织(36.95℃.36.21℃)和直肠(36.18℃,35.88℃)(P<0.01),对照组、nCDDPmm 和 nmm 未加 E 组各部位的温度无明显升高。14d 后,除 nCDDPmm+E 组肿瘤体积缩小外,其余各组的肿瘤体积增大4～15倍;各组肿瘤生长率分别为600%,—63%,139%,428%,598%(P<0.01)。nCDDPmm+E 组肝癌细胞大面积坏死(70%以上)。癌灶及癌边缘可见到栓塞的微球,其余各组的肝癌细胞中到轻度坏死(0～70%),正常肝组织未见明显的微球和坏死。结论交变电磁场可以通过诱导兔 VX_2肝癌靶区栓塞 nCDDPmm 和 nmm 的温度升高,介导靶区温度升高达43℃以上,磁介导的热疗对顺铂化疗有明显的协同作用。

Objective To investigate the effects of embolization thermochemotherapy induced by an alternating electromagnetic field mediated nano-ferroferric oxide cis-diammine-dichloroplatium magnetic microspheres （nCDDPmm） on rabbit VX2 liver tumor. Methods The rabbits with implanted VX2 carcinoma in the left liver lobe were randomized into 5 groups. In group A, the rabbits received a hepatic arterial infusion of saline and then exposed to an 40kHz and 24kA/min external alternating electromagnetic field （E） for 30 min. In group B, the animals received nCDDPmm （ferric oxide 30 mg/kg, CDDP 2 mg/kg） and E; In group C, the animals were given nano-ferroferric oxide microspheres （nmm, ferric oxide 30 mg/kg） and E. In group D, the animals received nCDDPmm but no E. In group E, the animals received nmm but no E. The temperatures in the center, margin of tumor, normal liver parenchyma （in the right lobe） and rectum were recorded with optical fiber transducer thermometer. The volume and growth rate of the tumors were moni- tored and the pathology of the tumors and normal livers observed 14 d after the treatment. Results In group B and C, the temperatures were significantly higher in the center and margin of tumor than in the normal liver parenchyma and rectum （P〈0. 01）. The volume and growth rate of the tumor were markedly decreased （P〈0.01）. There was massive necrosis in the tumor in group B 14 d after the treatment. Magnetic microspheres were seen in the tumor and margin of tumor. In other groups, the tumor volume was increased for 4 --15 times, growth rate of the tumor increased by 139%-600 % and there was only slight or middle necrosis in the tumor （0-70%）. Conclusions The temperature of the target area can be increased to 43℃ or over by E-mediated nCDDPmm or nmm targeted embolization to enhance the anti-tumor effect of CDDP.