The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma
The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma
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DOI：
10.1007/s11060-005-9059-z
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发表时间：
2006-05-01
影响因子：
3.9
通讯作者：
Felix, R
中科院分区：
文献类型：
--
作者：
Jordan, A;Scholz, R;Felix, R
磁性纳米粒子热疗是一种基于超顺磁性纳米粒子的磁场诱导激发的组织间热疗和热消融新技术。为了评估这种技术微创治疗的潜力，我们在大鼠肿瘤模型中对其对实验性多形性胶质母细胞瘤的影响进行了系统分析。通过将RG-2细胞植入120只雄性Fisher大鼠的脑中诱导肿瘤。将动物随机分配至10组，每组12只大鼠，包括对照组。动物接受两个热疗治疗后，单次瘤内注射两种不同的磁流体（葡聚糖或氨基硅烷涂层的氧化铁纳米粒子）。在肿瘤诱导后第4天和第6天，使用在100 kHz频率和0-18 kA/m可变场强下操作的交变磁场施加器系统进行治疗。通过动物的存活时间和脑和肿瘤的组织病理学检查来确定治疗的有效性。与对照组相比，氨基硅烷包被的纳米颗粒的热疗导致存活延长了4.5倍，而葡聚糖包被的颗粒没有显示出任何优势。发现氨基硅烷涂覆的颗粒的瘤内沉积是稳定的，允许连续热疗治疗而无需重复注射。治疗后的组织学和免疫组化检查显示，大坏死区接近颗粒沉积物，增殖率下降和反应性星形胶质细胞增生邻近肿瘤。因此，局部间质热疗与磁性纳米粒子具有抗肿瘤作用的恶性脑肿瘤。该方法适合于临床应用，并可能成为治疗目前无法成功治疗的恶性胶质瘤的新策略。最佳治疗方案和与其他疗法的潜在组合需要在进一步的研究中确定。
Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model. Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0-18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor. Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor. Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.