田口穩健法優化磁流體之合成條件及其應用在熱治療之研究
田口穩健法優化磁流體之
合成條件及其應用在熱治療之研究
張國平1 林智遠2 洪茂欽1 蔡長書1 李尚熾3 謝柏滄4
1慈濟技術學院放射醫學科學研究所
2核能研究所化學組
3中山醫學大學醫學影像暨放射科學系
4中台醫護科技大學放射科學研究所
摘要
熱治療通常被歸類在放射生物領域，而其治療方式當中，有一種是使用磁流體，曝露在交流電磁場中而使之加熱，其為本研究主要嘗試的方法。我們希望得到在交流磁場下能容易地加熱且對於腫瘤治療有效的磁流體。除此之外，我們使用田口穩健法來優化磁流體的製備參數。
利用共沉法合成磁鐵礦奈米粒子與適當地表面修飾後，在交流磁場作用下，溫度的上升速度隨著磁流體濃度與磁場強度增加而增加。且對於經過表面修飾的磁流體比未經修飾的產熱率（SAR）高。然後，上升的溫度最後會與周圍環境達到平衡狀態。TEM 的影像顯示我們合成的粒子平均粒徑為13 nm。XRD 實驗證實其磁性奈米粒子為Fe3O4 晶型。從SQUID 測出來的磁滯曲線，得知粒子具有超順磁性特徵。表面電位分析結果顯示，粒子表面帶正電荷。此外，MRI 影像顯示出奈米粒子滯留在腫瘤中。動物實驗顯示利用本研究之磁性奈米粒子進行的熱治療，對於腫瘤生長有抑制的效果。
關鍵字：田口穩健法、磁流體、熱治療
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Optimization of Ferrofluid by Using Taguchi Method and
Its Application in Hyperthermia
Kwo-Ping Chang1 Chih-Yuan Lin 2 Mao-Chin Hung 1
Chang-Shu Tasi1 Shan-Chih Lee3 Bor-Tsung Hsieh4
1 Institute of Radiological Sciences, Tzi-Chi College of Technology
2Chemical Division, Institute of Nuclear Energy Research
3School of Medical Imaging and Radiological Sciences, Chung-Shan Medical University, Taiwan
4Institute of Radiological Science, Central Taiwan University of Science and Technology, Taiwan
Abstract
Hyperthermia treatment of tumors is a promising branch of radiobiology. One hyperthermia treatment approach uses ferrofluid with an alternating current ( AC ) magnetic
field. This study sought to determine the ferrofluid ratio of Fe2+/Fe3+ and the desired reaction conditions which could produce a suspension of nanoparticles having the optimum SAR for use when applying the AC magnetic field method in tumor treatment. Magnetite nanoparticles were prepared based on co-precipitating and proper surface-treatment. When ferrofluids are exposed to an AC magnetic field, the temperature rises quickly, and is relative to the Fe3O4 concentration within the suspension and the intensity of the magnetic field. By means of surface treatment by surfactant, SAR values of the magnetite particles can be greatly enhanced. Under stable conditions, the induced temperatures ultimately remain constant due to the balance of heat generation and heat transfer to the surroundings. Analysis by Taguchi Method determined the optimal parameters for synthesizing a suspension generating the highest SAR value. The nanoparticle suspension with highest SAR was then tested in vivo using mice to confirm its effectiveness in treating the tumors. The TEM results showed the mean diameter of our synthesized nanoparticle was 13 nm. XRD verified the chemical form is Fe3O4. SQUID showed our particle is superparamagnetic from the magnetic hysteresis. Zeta potential analysis justified the magnetite nanoparticle surface has a positive charge, an accepted indicator for the –NH + 3 form. Additionally, upon in vivo testing, the MRI showed the nanoparticles were mostly confined to the tumor area. In conclusion, in clinical applications using AC magnetic field hyperthermia treatment to suppress the growth of tumors, our results offer a more efficient method of synthesizing the optimal ferrofluid suspension.
Keywords：Taguchi method, Ferrofluid, Hyperthermia
