製備功能性鐵鉑奈米微粒應用於癌症治療

Preparation of Functionalized FePt Magnetic Nanoparticles for Cancer Treatment

楊斯帆(Szu-Fan Yang)

指導教授 ： 鍾仁傑

國立臺北科技大學/工程學院/化學工程研究所/碩士(2014年)

https://doi.org/10.6841/NTUT.2014.00756

摘要

鐵鉑磁性奈米顆粒除了應用於磁性儲存媒體上以外，近年來更應用於生醫領域。鉑本身性質和金很接近，具有良好的生物相容性、無生物毒性、化學穩定性；而鐵為磁性優良的金屬，所以鐵鉑奈米合金是結合兩者優點。本研究是利用化學合成法去製備鐵鉑磁性奈米顆粒，並採用低毒性方式表面修飾2-氨基乙烷硫醇(SH)，再利用簡單製程將葉酸拮抗劑 (Methotrexate，MTX) 接上，製備出具有磁性導引、癌症細胞標定以及磁致放熱之多功能奈米磁性顆粒。以化學合成法合出來的FePt為疏水性奈米粒子，由成份分析出來得知鐵與鉑比為58:42，在20000G的磁場下飽和磁化量為12.58 emu/g，在室溫下為超順磁。由細胞毒性測試可以得知濃度為400 μg/mL對老鼠纖維母細胞(L929)沒有明顯毒性。以2-氨基乙烷硫醇修飾FePt後，利用FT-IR得知於3400 cm-1有明顯OH官能基，表示成功修飾成親水性。之後將MTX接上奈米粒子上，由UV/VIS以及FT-IR證明成功接枝上MTX。將FePt-MTX做細胞毒性測試，發現濃度為0.075 mg/ml以下為安全使用劑量，最後將FePt於交流磁場下做藥物制放，MTX釋放量隨時間增長而增加，代表可以透過高週波之控制達到藥物制放的目的。

關鍵字

鐵鉑磁性奈米顆粒 ； 葉酸拮抗劑 ； 磁滯放熱 ； 藥物制放

並列摘要

In addition to application in storage media, iron-platinum magnetic nanoparticles are also used in biomedical field in recent years. The nature of platinum resembles greatly from that of gold, including great biocompatibility, no toxicity and chemical stability. Iron metal has excellent magnetic ability. Hence, iron-platinum magnetic nanoparticles combine advantages of both elements. The aim of this study was to develop iron-platinum magnetic nanoparticles using chemical synthesis method and low-toxic way through modifying the surface by 2-aminoethane thiol (SH). And then a simple process was used to graft methotrexate (MTX) to achieve the preparation of multi-functional magnetic nanoparticle including magnetic guidance, cancer cell targeting and magnetic hyperthermia. The hydrophobic FePt alloy nanoparticle was prepared by chemical synthesis, and the proportion of iron and platinum was measured to be 58:42. It’s superparamagnetic at room temperature and the saturated magnetization was 12.58 emu/g under 20000 G magnetic fields. The toxicity of FePt was low for mouse fibroblasts cell line (L929) below concentration of 400 μg/mL. After surface modification by 2–aminoethane, we used FT-IR to prove the existence of OH functional groups in 3400 cm-1, which standing for the successful modification to become hydrophilic. Methotrexate (MTX) was further grafted on to the nanoparticle. The successful grafting of MTX was proved the by FT-IR and UV/VIS. Through cytotoxicity testing, we discovered that the safe dosage of FePt-MTX was below 0.075 mg/ml. Finally, drug release from FePt-MTX was investigated under AC magnetic field, and the results showed that the release of MTX increased with time. The goal of controlled drug release using high-frequency wave generator was achieved.

並列關鍵字

Iron-platinum magnetic nanoparticles ； Methotrexate ； Magnetic hyperthermia ； Controlled drug release

參考文獻

1. 馬振基, 奈米科技材料原理與應用. 2012.

3. Bian, B.R., et al., Effect of H-2 on the Formation Mechanism and Magnetic Properties of FePt Nanocrystals. Ieee Transactions on Magnetics, 2013. 49(7): p. 3307-3309.

5. 何建新, FePt奈米微粒之製備與自組裝特性研究 ，碩士論文，國立清華大學材料科學工程研究所，新竹，2004.

8. Gu, H.W., et al., Biofunctional magnetic nanoparticles for protein separation and pathogen detection. Chemical Communications, 2006(9): p. 941-949.

9. Chou, S.W., et al., In Vitro and in Vivo Studies of FePt Nanoparticles for Dual Modal CT/MRI Molecular Imaging. Journal of the American Chemical Society, 2010. 132(38): p. 13270-13278.