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Title: | 複合磁性奈米粒子Fe3O4/γ-Fe2O3核殼結構對磁誘導發熱於癌症熱療之探討 Effects of Fe3O4/γ-Fe2O3 core/shell structure of composite magnetic nanoparticles on magnetic induction heating for cancer hyperthermia |
Authors: | Shih-Chi Lee 李思圻 |
Advisor: | 傅昭銘(Chao-Ming Fu) |
Keyword: | 磁性奈米粒子,核殼結構,磁性異向性,界面耦合,磁滯損耗,磁誘導發熱,微脂體包覆,熱炙治療,癌症治療, magnetic nanoparticle,core-shell structure,magnetic anisotropy,interfacial coupling,hysteresis loss,magnetic induction heating,liposome-coated,hyperthermia,cancer therapy, |
Publication Year : | 2014 |
Degree: | 博士 |
Abstract: | 磁性奈米粒子在生醫領域已引起了高度的興趣,例如磁誘導熱炙治療、磁振造影、標靶藥物遞送、放射性標的標靶等皆是目前其相關研究的主題。磁誘導熱炙治療係利用磁性奈米粒子對局部部位的腫瘤組織進行熱炙治療且可降低對其周圍正常組織的傷害,是一種極具潛力的癌症治療技術。本研究針對已獲美國食品暨藥物管理局認證且批准具生物相容性Fe3O4與γ-Fe2O3的磁性奈米粒子展開調查。一般而言,磁性奈米粒子常藉由控制粒子的尺寸及賦予特殊的特性而提升其發熱能力。然而已有文獻表示,純Fe3O4的磁性奈米粒子對於磁誘導發熱有物理的極限。近年亦有文獻顯示,核殼磁性奈米粒子的磁異向性可藉由核與殼的磁性交互耦合進行調變,進而達到提高其對治療功效的發熱功率。
本研究在室溫下以化學共沉澱法合成與表面修飾處理,製備得具尺寸分佈的Fe3O4/γ-Fe2O3核殼磁性奈米粒子,並檢驗Fe3O4/γ-Fe2O3核殼磁性奈米粒子的組成結構、成分比例、幾何特徵以及磁學特性。研究中顯示,Fe3O4/γ-Fe2O3 核殼磁性奈米粒子在弱交變磁場下展現前所未有的高效率磁誘導發熱能力。並且我們可注意到,隨著當外加的交變磁場越大,磁性奈米粒子將會彼此產生聚集,使得其發熱能力會受到抑制。 為了分析核殼磁性奈米粒子的磁誘導發熱特性,本研究建立一套非線性磁化相依的磁滯模型進而比較所有的實驗結果。對於這個理論模型,我們僅考慮磁異向能與真實尺寸分佈,所得到的平均磁化強度及磁滯損耗功率皆可吻合實驗的結果。由此模型可分析一個核殼磁性奈米粒子的等效磁異向性,以探討磁異向性對磁誘導發熱的影響,進而討論磁異向性與發熱機制的關聯性。從理論模型分析結果顯示,核殼磁性奈米粒子的核殼界面交互作用可顯著地提升其磁誘導發熱的能力。除此之外,核殼的成分比例亦對於磁誘導發熱亦有顯著的影響。這些因素皆有助於提升磁性奈米粒子的磁誘導發熱能力,以改善癌症熱炙治療的效益。 本研究更進一步地將高效率發熱的核殼磁性奈米粒子進行表面改質,並結合奈米微脂體而得核殼磁性奈米微胞,以對於小鼠結腸癌細胞進行細胞內熱炙治療。從實驗結果顯示,由於具有良好生物相容性的核殼磁性奈米微脂體將會被癌細胞內吞,並在某容許的攝取劑量下不會影響細胞的生理機制與產生毒理反應。而更進一步地對於攝取核殼磁性奈米微脂體的癌細胞,在僅15 Oe、89 kHz的弱交變磁場的作用下有顯著的減少趨勢,可成功地達到細胞內熱炙治療的效果。 Magnetic nanoparticles are widely used for biomedical applications, such as magnetically induced hyperthermia, magnetic separation of bio-entities, contrast agents in magnetic resonance imaging and magnetic targeting of chemotherapeutic drugs. Magnetically induced hyperthermia is one of the most promising techniques for cancer treatment. This technique makes use of localized magnetic nanoparticles thus reducing injuries to the surrounding healthy tissues. In this study, we have investigated magnetic nanoparticles of both magnetite and maghemite. Both materials are approved as compatible magnetic materials for humans by the U.S. Food and Drug Administration (FDA). In general, the heating capabilities of magnetic nanoparticles can be improved by controlling particle size and endowing them with special properties. However, magnetic nanoparticles of pure magnetite have revealed that physical limits exist in magnetically induced heat generation. In recent years, magnetic anisotropies of core-shell magnetic nanoparticles were shown to be modulated by mutual coupling of magnetic hard and/or soft components to promote the magnetic induction heating power for therapeutic efficacy. The size-distributed Fe3O4/γ-Fe2O3 core/shell magnetic nanoparticles were synthesized by a method of chemical coprecipitation and surface modification at 300 K in this study, and their chemical composition, structure, proportion of components, dimensional features and magnetic properties were examined. The experimental results shows that the core-shell magnetic nanoparticles have an unprecedented efficient heating performance under a weak alternating magnetic field. Moreover, we observed that the core-shell magnetic nanoparticles aggregate to restrain the increase in their magnetic induction heating power when the applied alternating magnetic field increases. This study uses the rate-dependent hysteresis model to compare the experimental results in order to analyze the physical factors which contribute to magnetic induction heating. For this model, we consider the magnetic anisotropies and an actual size distribution to calculate average magnetization and hysteresis power loss, which almost fits our experimental results. The effective magnetic anisotropy of a core-shell magnetic nanoparticle can be analyzed by this model to clarify the significant effect seen upon magnetically induced heat generation and to obtain their relationship. According to the theoretical results analyzed, the magnetic interfacial coupling between the magnetite-core and the maghemite-shell can strongly promote the magnetically induced heat generation. In addition, the proportion of magnetite-core and maghemite-shell has a significant impact on magnetic induction heating as well. Both significant factors are conducive to promote the magnetically induced heating performance of core-shell magnetic nanoparticles for improving the hyperthermic efficiency of cancer treatment. We further performed surface modification and conjugated cationic liposomes to the core-shell magnetic nanoparticles and obtain biocompatible core-shell magnetic micelles of 124 nm. Mouse colon carcinoma cells (CT-26 cells) were treated with these core-shell magnetic micelles for intracellular magnetically induced hyperthermia. From the experimental observation, the core-shell magnetic micelles were ingested by CT-26 cells, which under a certain tolerable accumulated dosage did not affect cellular physiology and did not show any signs of cytotoxicity. The CT-26 cells which ingest the core-shell magnetic micelles were shown to undergo cell death under a weak alternating magnetic field of 10 Oe, 89 kHz, thus successfully accomplishing intracellular magnetically induced hyperthermia. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16831 |
Fulltext Rights: | 未授權 |
Appears in Collections: | 物理學系 |
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