本研究合成具有高比吸收率(specific absorption rate, SAR)之含釓氧化鐵磁性奈米粒子(Gd-doped iron oxide nanoparticle，GdIONP)，探討GdIONP磁熱性質，以及改變合成條件中Gd:Fe比例對奈米粒子粒徑及比吸收率(SAR)之影響。合成顆粒組成從Gd0.01Fe2.99O4至Gd0.04Fe2.96O4，平均磁奈米粒子粒徑為12nm至33nm。其中Gd0.03Fe2.97O4 在交互磁場強度246 Oe和52 kHz作用下產生磁熱效應，比吸收率（SAR）約為38Wg-1 [Fe]，相較Fe3O4組成之氧化鐵奈米粒子的SAR值高出約4倍，且同時具有T2-weighted 磁振造影 (MR imaging)，為一同時具有診斷及治療之多功能性奈米粒子。並進一步以小鼠腫瘤模式探討GdIONP於腫瘤熱治療效果，以小鼠前列腺癌（TRAMP-C1）腫瘤模式測試結果顯示GdIONP能縮小腫瘤大小及延遲腫瘤生長，更進一步將GdIONP磁熱治療結合放射線治療，結合治療能有效減緩腫瘤生長增加治療效果，同時探討GdIONP對腫瘤微環境影響，GdIONP於腫瘤磁熱治療中同時存在熱剝蝕(thermal ablation)及溫熱治療(mild hyperthermia)，高溫熱剝蝕效應(>45°C)能直接損壞腫瘤血管使腫瘤細胞壞死，溫熱治療區(39~42°C)則能增加腫瘤血流及減少缺氧區域，增加結合放射線治療效果。

Recent advances in nanotechnology have contributed to the development of multifunctional nanoparticles as representative nanomedicine. Among different kinds of nanomaterials, iron oxide nanoparticles are among the most promising candidates in combining imaging and therapeutics functions in a single, multimodal platform. This study aimed to develop magnetic nanoparticles to produce heat in the presence of an applied alternating magnetic field, evaluate its therapeutic effects in mouse model and investigate the adjuvant effect for radiotherapy. Gadolinium-doped iron oxide nanoparticles (GdIONPs) were developed for use in tumor therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 with the average magnetic core diameters to be 12nm and 33nm respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38 Wg−1 [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4.
The heating rate for the nanoparticles in vivo and the potential for tumor therapy were determined in a mouse prostate tumor model, transgenic adenocarcinoma of the mouse prostate C1 (TRAMP-C1). The intramuscular TRAMP-C1 tumor treated with doped iron oxide displayed much slower tumor growth. The particle tracking were also demonstrated by MR imaging and laser ablation/inductively coupled plasma (LA-ICP-MS) mapping. The GdIONPs accumulated in tumor region during the treatment could be clearly tracked and quantified by T2-weighted MR imaging and LA-ICP-MS mapping. The therapeutic effects of GdIONP-mediated hyperthermia alone or in combination with radiotherapy were also evaluated. A significant increase in the tumor growth delay was observed following the treatment of thermotherapy only group (2.5 days), radiation therapy only group (4.5 days), and the combined radio-thermotherapy group (10 days). Immunohistochemical staining revealed a reduced hypoxia region with vascular disruption and extensive tumor necrosis following the combined radio-thermotherapy. These results indicate that GdIONP-mediated hyperthermia can improve the efficacy of radiotherapy by its dual functions in high temperature (temperature greater than 45 °C)-mediated thermal ablation and mild-temperature hyperthermia (MTH) (temperature between 39 ~ 42 °C)-mediated reoxygenation.

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