Fundamental study on gene-hyperthermia for cancer using heat sensitive gene

本文研究了以磁铁矿颗粒为加热材料的肿瘤热疗。在本研究中，热疗不仅通过单独加热进行，还与基因表达和药物掺入相结合。为了增加癌细胞上吸附的磁铁矿的量，将带正电荷的脂质TMAG掺入到磁脂质体中。制备了聚乙二醇包被的磁铁矿颗粒，经尾静脉给药后，通过磁共振成像观察其肿瘤组织的数量。研究发现，这些颗粒可用作磁共振造影剂。将干扰素β基因布置在热诱导启动子下游，制备了携带该基因的脂质体。将基因包裹的脂质体导入脑胶质瘤细胞，获得了瞬时表达的干扰素-β。为了增强热疗的杀灭效果，将自制的磁脂质体直接注射到大鼠皮肤下的肿瘤组织中。经386Oe的高效磁场照射40min后，取脑组织进行组织学观察。结果发现，经3次治疗后，大鼠胶质瘤细胞几乎全部死亡。

Hyperthermia for cancer using magnetite particles as heating material has been studied. In the present study, hyperthermia was not performed only by heating alone but also by combination with gene expression and drug incorporation.In order to increase the amount of magnetite adsorbed to a cancer cell, TMAG which is a lipid with positive charge was incorporated to a magnetoliposome. Polyethylene glycol coated magnetite particles were prepared and those amount it tumor tissue was observed by means of Magnetic Resonance Imaging after administrated through a tail vein. It was found that those particles can be used as a magnetic resonance contrast agent. Interferon beta gene was arranged downstream heat inducible promoter and the liposome with the gene was prepared. When the gene-encapsulated liposome was incorporated to glioma cells, the transient expression of interferon-beta was obtained. In order to enhance the killing effect by hyperthermia, the magnetoliposome prepared by us was directly administrated to the tumor tissue, which formed under the skin of a rat. Glioma tissue was observed histologically after 40 min treatment by high efficiency magnetic field with 386 Oe. As a result, it was found that almost all rat glioma cells were dead after 3 times treatment.