磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性

目的：观察磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性，并观察磁性白蛋白纳米粒在各脏器中的分布特征。方法：建立大鼠移植性肝癌模型。大鼠正中开腹，胃十二指肠动脉插管固定。实验组，肝肿瘤区外加磁场，肝动脉注射磁性阿霉素白蛋白纳米粒(相当于阿霉素0．5mg／kg)，磁场应用30min，移去磁场后，动物立即处死。对照组肝肿瘤区不加磁场，肝动脉注射同样剂量的纳米粒后30min处死。动物处死后，立即取肿瘤组织、非磁区正常肝组织、心、肾、脾、肺、小肠和胃作了计数，肿瘤组织、肝组织送病理切片检查。结果：肝肿瘤区应用磁场30min后，磁区肿瘤组织的放射活性较非磁区肝组织的放射活性明显增加，磁区肿瘤组织的放射活性为非磁区正常肝组织的放射活性的8．7倍。对照组在没有磁场存在的情况下，肿瘤组织的放射活性为正常肝脏的2．8倍。实验组肺的放射活性较对照组明显降低。肾、心、脾、小肠和胃两组之间无明显差异。另外，实验组脾、肺和胃与肿瘤组织的放射活性之比较对照组大为降低。注入纳米粒800%以上分布于肝脏。结论：在磁场的作用下，磁性阿霉素白蛋白纳米粒在大鼠移植性肝肿瘤中的聚集明显增加。即使肝肿瘤区没有外加磁场，由于肿瘤组织和正常肝组织血管密度的差异，磁性阿霉素白蛋白纳米粒在肿瘤组织中的分布明显高于正常肝组织。实验组脾、肺、胃与肿瘤组织的放射活性比值大大低于对照组，说明磁场的存在使这些脏器的相对药物暴露明显降低。

Target distribution of magnetic albumin nanoparticles containing adriamycin in model of transplanted liver cancer in rats

Objective To investigate the effect of magnetic field application to target distribution of the nanoparticles in the model of transplanted liver cancer in rats. Methods Seven days after a model of transplanted liver cancer was established in rats, abdominal exposure was performed though a midline abdominal incision. A cannula was inserted into the gastro-duodenal artery. In the experimental group, the tumor tissue was exposed to the magnetic field for 30 min. Magnetic albumin nanoparticles containing adriamycin was injected into the hepatic artery (equivlent dose of free adriamycin 0.5 mg/kg). After the magnetic field was removed, the animals were immediately sacrificed. Administration of equal dose of nanoparticles in absence of magnetic field was employed to serve as the control. Tumor, non-target site of liver, heart, kidney, lung, spleen, stomach and small intestine were analyzed for 125I-counts. The tumor and liver tissue were examined for histological changes. Results In the experimental group, the radioactivity of the tumor tissue was 8.7 times as high as that of the liver tissue. In the control group, the radioactivity of tumor tissue was 2.8 times as high as that of normal liver tissue. The radioactivity of the lung was greatly reduced in the experimental group as compared with the control group. There was no significant difference in the radioactivity in kidney, heart, spleen, small intestine and stomach between the 2 groups. Meanwhile, over 80% of the injected radioactive dose of nanoparticles was found in the liver. Conclusions In the presence of magnetic field, magnetic albumin nanoparticles accumulated in tumor tissue. The lung, spleen and stomach in the experimental group are less exposed to chemotherapeutic drug than those in the control.