Department of Organ Regenerative Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
AdMeTech Co., Ltd., Matsuyama, Ehime, Japan.
Int J Cancer. 2010 Apr 15;126(8):1955-1965. doi: 10.1002/ijc.24864.
Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel-embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb-c/nu/nu mice. Various concentrations of docetaxel-embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite-loaded liposome (ML)-injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43 degrees C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 microg/ml, while a docetaxel concentration > 568.5 microg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent-embedded magnetoliposomes has an anticancer effect.
热疗是一种针对癌症的微创治疗方法,但很难实现只加热肿瘤而不损伤周围组织。为了解决这个问题,我们研究了载多西紫杉醇磁脂质体(DML)和外加交流磁场的化疗热疗的有效性。将人 MKN45 胃癌细胞植入 Balb-c/nu/nu 小鼠的后肢。将不同浓度的载多西紫杉醇 DML 注入肿瘤并暴露于交流磁场下(n = 6,每组)。为了与单纯热疗进行比较,将载磁铁矿脂质体(ML)注入的肿瘤暴露于交流磁场下。此外,还比较了无交流处理的 DML 和用交流处理稀释于 PBS 中的多西紫杉醇的结果(n = 10,每组)。肿瘤表面温度保持在 42 到 43 摄氏度之间。在 DML 浓度 > 56.8 μg/ml 的组中,肿瘤体积减小,而在无热疗的情况下,需要 DML 浓度 > 568.5 μg/ml 才能减小肿瘤体积。在接受磁场的 DML 组与其他组之间,肿瘤体积和存活率存在统计学显著差异。在接受磁场的 DML 组中,3 只小鼠的肿瘤消失;2 只小鼠在治疗后存活超过 6 个月,而其他组的所有小鼠均在 15 周内死亡。组织学上,DML 热疗破坏了肿瘤细胞,并且 DML 均匀扩散。据我们所知,这是首次报道显示载化疗药物磁脂质体的热疗具有抗癌作用。