Kikumori Toyone, Kobayashi Takeshi, Sawaki Masataka, Imai Tsuneo
Department of Breast and Endocrine Surgery, Nagoya University Hospital, Showaku, Nagoya, Japan.
Breast Cancer Res Treat. 2009 Feb;113(3):435-41. doi: 10.1007/s10549-008-9948-x. Epub 2008 Mar 2.
We have constructed anti-HER2 immunoliposomes containing magnetite nanoparticles (HML) that generate heat in an alternating magnetic field (AMF). The effective targeting and cytocidal abilities of HML have been achieved using cell culture models. This study aimed to investigate feasibility of this modality for breast cancer treatment using tumor-bearing mouse models.
The subcutaneous cancer nodules of BT474 (high HER2 expression) or SKOV3 (low HER2 expression) cells in nude mice were employed as models. HMLs were injected into these cancer nodules and were then exposed to an AMF for 30 min twice at 24 h intervals. Accumulation of magnetite and tumor growth rates were examined. Histological findings of the thermal effect were also examined.
HMLs accumulated in only BT474 tumors. The tumor temperature increased to 45 degrees C whereas the body temperature remained at around 38 degrees C. Tumor regression was observed in the hyperthermic group and was sustained for 10 weeks after hyperthermia.
These results suggest that hyperthermia using HML is an effective and specific therapy for breast cancer overexpressing HER2. This therapy may provide an alternative way to treat recurrent cancer refractory to other modalities.
我们构建了含有磁铁矿纳米颗粒的抗HER2免疫脂质体（HML），其可在交变磁场（AMF）中产生热量。利用细胞培养模型已实现了HML的有效靶向和杀细胞能力。本研究旨在使用荷瘤小鼠模型研究这种治疗方式用于乳腺癌治疗的可行性。
以裸鼠体内BT474（HER2高表达）或SKOV3（HER2低表达）细胞的皮下癌结节作为模型。将HML注射到这些癌结节中，然后每隔24小时暴露于AMF中30分钟，共两次。检测磁铁矿的蓄积和肿瘤生长速率。还检查了热效应的组织学结果。
HML仅在BT474肿瘤中蓄积。肿瘤温度升至45℃，而体温维持在38℃左右。在热疗组观察到肿瘤消退，且在热疗后持续10周。
这些结果表明，使用HML进行热疗是治疗HER2过表达乳腺癌的一种有效且特异性的疗法。这种疗法可能为治疗对其他方式难治的复发性癌症提供一种替代方法。
