鐵-金奈米合金之合成與生醫應用研究鐵-金奈米合金之合成與生醫應用研究

Study of Iron-Gold Alloy nanoparticle for Biomedical Application

吳國廷(Kou-Ting Wu)

指導教授 ： 鍾仁傑

國立臺北科技大學/工程學院/工程科技研究所/碩士(2012年)

摘要

本研究旨在發展鐵-金合金奈米粒子(NFA)，此材料具超順磁性可應用在生醫相關領域，例如藥物制放或作癌症熱治療。以熱裂解法合成出來的NFA在二次水中有很好的分散性，由成份分析得知其鐵與金的莫耳比約為2：1，平均粒徑約為3.932 nm，在20 KOe的磁場下飽合磁化量為 3.5 emu/g，且在室溫下為超順磁性。由細胞毒性測試可以得知500 μg/mL對老鼠纖維母細胞(L929)及人類肝癌細胞(Hep-G2)沒有明顯毒性。葉酸拮抗劑(MTX)為一抗癌藥物，並可用以標定癌症細胞，為了在NFA表面接枝MTX，先在NFA表面修飾2-氨基乙烷硫醇(SH)，再利用SH上的胺基與MTX上的羧基形成醯胺鍵，成功完成在NFA上接枝MTX，並可以透過傅立葉轉換紅外線光譜儀檢測加以驗證。為了證明NFA-MTX能有效標定癌症細胞，透過ICP測量Hep-G2對NFA-MTX的食入量，發現NFA-MTX的食入量為0.789 pg/cell，約為L929對NFA-MTX的1.5倍，由此推論出在NFA-MTX對Hep-G2有標靶性。NFA在高週波(頻率:700~1100KHz)下產生熱能，經過計算每一顆NFA可以產生2.03×10-16焦耳的熱能。經施加高週波(頻率:700~1100KHz，反應時間20分鐘)，Hep-G2在NFA濃度為200μg/mL的條件下，其細胞存活率大約下降了45％，代表此材料可以應用於作癌症治療；研究中發現高週波處理產生的熱能可打斷NFA與MTX間的鍵結，經不同的高週波操作時間，可發現MTX的釋放量隨時間變長而增加，代表可以透過高週波之控制達到藥物制放的目的。

關鍵字

鐵-金合金奈米粒子 ； 磁性奈米材料 ； 熱治療 ； 藥物制放

並列摘要

The aim of this study is to develop Iron-Gold Alloyed nanoparticles (NFAs), which are superparamagnetic and of great potential to be applied in the biomedical fields, including hyperthermia treatment for cancer and drug controlling release. The NFAs were prepared through a pyrolysis method and well dispersed in distilled water. The ratio of iron to gold was 2 : 1 through analyzing. The mean diameter was 3.932 nm. The saturated magnetization was 3.5 emu/g under 20 KOe magnetic field. The material was superparamagnetic at room temperature. The result of in vitro tests showed that under a dose of 500μg/mL were not cytotoxic to L929 cell and Hep-G2 cell. Methotrexate (MTX) is an anti-cancer medicine and able to target the cancer cells. MTX was further conjugated on to NFA through a series of chemical modifications, including 2-aminoethanethiol grafting, and then the amine bonded with the carboxyl group on MTX to form an amide bond. Immobilization of MTX on the NFA was confirmed using FTIR. The uptake of Hep-G2 cells was 0.789 pg/cell for NFA-MTX, which was 1.5 times of the L929 cells. The results indicated the targeting efficiency of NFA-MTX to cancer cells. After calculation, per NFA would generate a 2.03×10-16 J heat under a high frequency magnetic field (700 to 1100)KHz. After treating with 200μg/mL NFA-MTX and then being applied a (700 to 1100) KHz high frequency magnetic field treatment for 20 minutes, the residual viability of Hep-G2 cells dramatically decreased 45%. Besides, we also discovered that the releasing of MTX from NFA-MTX was dependent with the applied time of high frequency magnetic field. The generated heat was able to break the amide bonds between NFA and MTX. The release of MTX could be successfully controlled. Using NFA-MTX, a hyperthermia treatment and drug controlling release will be achieved under high frequency alternating magnetic field.

並列關鍵字

Iron-gold alloy ； magnetic material ； drug delivery ； hyperthermia

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