Kato Shinya, Kimura Masatsugu, Kageyama Katsuhiro, Tanaka Hiroshi, Miwa Nobuhiko
Radioisotope Centre, Osaka City University Graduate School of Medicine, Asahimachi 1-4-3, Abeno-ku, Osaka, 545-8585, Japan.
J Nanosci Nanotechnol. 2012 Jun;12(6):4472-7. doi: 10.1166/jnn.2012.6180.
The nitroimidazole-related hypoxic radiosensitizer, pimonidazole (Pmz) was encapsulated in liposome composed of dipalmitoylphosphatidylcholine, cholesterol and dipalmitoylphosphatidylglycerol (molar ratio = 1:1:0.2; diameter = 112.9 nm), and the radiosensitization was evaluated in human melanoma cells HMV-II. Cell proliferation was examined by WST-8 assay after X-ray irradiation in the presence of liposomal Pmz or free-Pmz under hypoxic conditions. On 7th day after X-ray irradiation of 5 Gy, cell proliferation decreased more markedly in the administration of liposomal Pmz than free-Pmz at equivalent Pmz doses. Chromatin fragmentation or nuclear condensation was observed in liposomal Pmz-treated HMV-II cells. Radiosensitization was enhanced dose-dependently along with Pmz amounts of 250-2000 microM contained in liposomal Pmz. Intracellular uptake was more abundant for liposomal Pmz for 60-240 min than for free-Pmz. Thus liposomal Pmz has a potential to overcome radiation resistance in hypoxia, owing to enhanced intracellular uptake by melanoma cells.
将硝基咪唑类乏氧放射增敏剂匹莫硝唑（Pmz）包裹于由二棕榈酰磷脂酰胆碱、胆固醇和二棕榈酰磷脂酰甘油组成的脂质体中（摩尔比 = 1:1:0.2；直径 = 112.9 nm），并在人黑色素瘤细胞HMV-II中评估其放射增敏作用。在乏氧条件下，于脂质体Pmz或游离Pmz存在的情况下进行X射线照射后，通过WST-8法检测细胞增殖情况。在5 Gy X射线照射后的第7天，在等效Pmz剂量下，脂质体Pmz给药组的细胞增殖比游离Pmz给药组下降更明显。在脂质体Pmz处理的HMV-II细胞中观察到染色质断裂或核浓缩现象。随着脂质体Pmz中所含Pmz量在250 - 2000 microM范围内，放射增敏作用呈剂量依赖性增强。脂质体Pmz在60 - 240分钟内的细胞内摄取量比游离Pmz更丰富。因此，由于黑色素瘤细胞对脂质体Pmz的细胞内摄取增加，脂质体Pmz有潜力克服乏氧状态下的辐射抗性。
