磁性奈米粒子的電磁發熱特性與細胞體外熱炙之生醫應用

Induction heating properties of magnetic nanoparticles, and biomedical application for in vitro hyperthermia

李嘉偉(Chia-Wei Lee)

指導教授 ： 傅昭銘

國立臺灣大學/理學院/物理研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.10301

摘要

超順磁性四氧化三鐵(Fe3O4)奈米粒子近年來於生醫上應用的研究已有許多進展，主要為生物細胞分離、核磁影像檢測、標靶藥物導向、熱炙治療等生醫用途。除此之外，由研究顯示Fe3O4的磁性奈米粒子於交流磁場下具有良好的發熱特性，可作為臨床的腫瘤熱炙治療。本研究為了製作高效率發熱的Fe3O4磁性奈米粒子，便以化學共沉法製備，並控制滴定速率與pH值，再利用試劑洗滌進行表面電荷中和與修飾而得到一系列的磁性奈米粒子，其尺寸範圍為14 - 32 nm，而大多則約為21 nm，再分別將其以PEG-400進行包覆，將可得到為原來2 - 2.6倍大小的顆粒，其飽和磁化強度約為65 - 75 emu/g，矯頑磁力皆小於18 Oe，殘餘磁化量則小於3 emu/g。本研究利用100 kHz、10 Oe的射頻磁場進行發熱量測試，得知以酒精洗滌至pH ~ 3.5的磁性奈米粒子的發熱效率最佳，其比吸收率（SAR）高達23.98 W/g，SAR/Q達146.15 W/g。隨之再將磁性奈米粒子與腎癌細胞（RCC）混合，以100 kHz、15 Oe的射頻磁場進行熱炙試驗。其濃度為0.98 - 3.33 mg/ml 含有磁性奈米粒子的腎癌細胞樣本從37 ℃將加熱至41.2 - 47.5 ℃持續15分鐘（全程30分鐘），則腎癌細胞的存活率為82.3 % - 0 %。從醫學研究顯示，生物體不得暴露於核定範圍的射頻磁場中（H×f < 6.09×10^6 Oe/sec），因此本研究利用適當的射頻磁場（100 kHz、15 Oe）進行RCC細胞體外熱炙試驗而達到預期的效果。

關鍵字

四氧化三鐵 ； 磁性奈米粒子 ； 鬆弛損耗 ； 熱炙治療

並列摘要

The superparamagnetic Fe3O4 nanoparticles have been widely utilized for biomedical applications so far, such as for magnetically separating of bio-entities, contrast agents in magnetic resonance imaging, magnetically targeting of chemotherapeutic drugs, hyperthermia therapy, etc. Besides, the Fe3O4 nanoparticles have been shown superior heating properties under altering magnetic field, which implies hyperthermia therapy for clinical cancer treatment. In this study, we controlled the titration rate, pH and neutralized the surface charge by purging agents in order to synthesize the superparamagnetic Fe3O4 nanoparticles possessed superior heating properties. Their particle size are in the range of 14 - 32 nm with a mean size close to 21 nm, and the PEG-coated particle size are about 30 - 50 nm. Moreover, the saturation magnetization are about 65 - 75 emu/g, coercivity are less than 18 Oe, the residual magnetization are less than 3 emu/g. After the heating experiment under altering magnetic field of 100 kHz, 10 Oe, we could observe the superparamagnetic Fe3O4 nanoparticles, purged to pH~3.5 by alcohol, showed the optimal specific absorption rate (SAR) is 23.98 W/g, the quantity of SAR/Q is 146.15 W/g. In addition, we injected these superparamagnetic Fe3O4 nanoparticles into the cells culture medium of renal cell carcinoma (RCC), and applied the altering magnetic field of 100 kHz, 15 Oe to perform in vitro hyperthermia. This samples of RCC medium, concentration with Fe3O4 nanoparticles are in the range of 0.98 - 3.33 mg/ml, were heating from 37 ℃ to 41.2 - 47.5 ℃ for 30 min of whole course. However, the survival rates (SR) of RCC are from 82.3% to 0%. Furthermore, the biomedical studies had been shown the organisms can't be applied a radio-frequency (RF) magnetic field exceed the limitation of H×f < 6.09×10^6 Oe/sec, we utilized a proper RF magnetic field,100 kHz, 15 Oe, to achieve the prospective results in this study.

並列關鍵字

Fe3O4 ； magnetic nanoparticle ； relaxation loss ； hyperthermia

參考文獻

[11] 吳俊人, 利用聚乙二醇和葉酸接枝於石墨包覆鐵磁性奈米粒子做癌症之熱治療, 國立台灣大學醫學工程學研究所碩士論文 (2007).

[9] 陳志榮, 流體中奈米粒子自結合傳遞與釋放技術之研發, 國立成功大學機械工程研究所碩士論文 (2004).

[25] 蘇嘉弘, 溫度感應性共聚微乳膠與磁性材料結合應用於熱治療與藥物釋放系統之研究, 國立臺灣大學工學院高分子科學與工程學研究所碩士論文 (2007).

[76] S. W. Lee, S. Bae, Y. Takemura, I. Shim, T. M. Kim, J. Kim, H. J. Lee, S. Zurn and C. S. Kim, J. Magn. Magn. Mater. 310, 2868 (2007).

[5] F. Y. Cheng, C. H. Su, Y. S. Yang, C. S. Yeh, C. Y. Tsai, C. L. Wu, M. T. Wu and D. B. Shieh, Biomaterials 26, 729 (2005).