雙磷酸鹽-葡萄聚醣-四氧化三鐵磁性奈米粒子於生醫應用之特性研究

Characteristic studies of bisphosphonates-dextran-Fe3O4 composite nanoparticles for biomedical application

李効松(Siao-Song Lee)

指導教授 ： 婁世亮

中原大學/理學院/奈米科技碩士學位學程/碩士(2011年)

https://doi.org/10.6840/cycu201101112

摘要

摘要
本研究是以熱裂解抑制噬骨細胞數量的增長，減緩骨質疏鬆症惡化為目的。研究構思是噬骨細胞胞飲雙磷酸鹽/四氧化三鐵磁性複合奈米粒子，以射頻溫升複合奈米粒子，熱裂解噬骨細胞。粒子的合成方法是運用共沉澱法製備四氧化三鐵奈米粒子（FeNP），在其上，先以葡萄聚醣（dextran）與之交聯成Dex/FeNP，繼以雙磷酸鹽（bisphosphonate）結合成Dex/Bis/FeNP。FeNP、Dex/FeNP和Dex/Bis/FeNP都經由XRD和FT/IR確證合成成功；TEM及DLS雙重分析比對這些粒子之平均粒徑約為20 nm；FeNP 之SQUID飽和磁化量為81.7 emu；Dex/FeNP在水中之分散性極佳；所製備的粒子對RAW 264.7細胞株的MTT試驗結果指出，Dex/FeNP具有良好之生物相容性。在體內及體外之MRI成像探討的結果顯示，所製備之磁性奈米粒子具有顯影強化效果。經3,000高斯磁化6小時之1-mg/mL FeNP，在射頻（42 kHz，450 A）照射下20分鐘，約有20oC的溫升，足以熱裂解噬骨細胞。總言之，本研究成功製備出分散性極佳兼具射頻溫升特性之磁性奈米粒子，證實經磁化之磁性奈米粒子更具射頻溫升效果，並確證射頻可以熱裂解胞飲有Dex/Bis/FeNP之噬骨細胞，在減緩骨質疏鬆惡化之應用上具有潛能。

關鍵字

熱裂解 ； 射頻輻射 ； 磁化 ； 骨質疏鬆症 ； 磁性奈米粒子

並列摘要

Abstract
The goal of this study is to reduce the amount of osteoclasts by thermolysis to control osteoporosis aggravation. The idea is to synthesize bisphosphonate conjugated Fe3O4 nanoparticles engulfed by osteoclasts, which are lysed by temperature increase of the nanoparticles induced with radio frequency (RF) exposures. The particles of Fe3O4 were first synthesized by a chemical co-precipitation method and then were coated with dextran. The formed Dex/Fe3O4 particles were conjugated by bisphosphonate to become Bis/Dex/Fe3O4. The size of the Dex/Fe3O4 particles was verified by TEM and DLS and the results indicate that the average diameter of the particles was 20 nm approximately. All three kinds of nanoparticles had cubic inverse spinel structure of Fe3O4 in the XRD verification. FT-IR spectroscopy confirmed that the nanoparticles of Dex/Fe3O4 and Bis/Dex/Fe3O4 possessed the functional groups of dextran and bisphosphonate. The magnetization of the Fe3O4 nanoparticles by a SQUID magnetometer was 81.7 emu. In addition, the Dex/Fe3O4 nanoparticles can be fully dispersed in double distilled water. The cell line of mouse macrophages (RAW 264.7) was individually co-cultured with nanoparticles. The MTT assay study results indicated that these nanoparticles are cyto-toxicity free. Both in vitro and in vivo MRI showed that the image contrast was enhanced by the Dex/Fe3O4 nanoparticles. An RF system (42 kHz and 450 A) was used to raise the temperature of the nanoparticles. A test sample containing 1-mg Fe3O4 nanoparticles in 1-mL double distilled water magnetized by a 3,000-gauss magnet for six hours received the RF exposures for 20 minutes. A temperature rise of 20 oC was observed approximately. This thermal effect is sufficient to destroy osteoclasts. In conclusion, this work has successfully developed the magnetic nanoparticles that can be well dispersed in water and can be induced thermal effect by RF. Such an effect can be further enhanced by magnetizing the nanoparticles. It is believed that the Bis/Dex/Fe3O4 nanoparticles have the potential to be applied in controlling osteoporosis.

並列關鍵字

Osteoporosis ； Radio frequency ； Magnetization ； Magnetic nanoparticles ； Thermolysis

參考文獻

[51]. 巫珮如. 射頻輻射對蝕骨細胞胞飲磁性奈米粒子之熱效應探討. 中原大學生物醫學工程學系碩士學位論文. 民國97年.

[3]. Figuerola, Albert. From iron oxide nanoparticles toward advanced iron-based inorganic materials designed for biomedical applicatios. Pharmacological Research. 2010, Vol. 62, pp. 126-143.

[5]. Massart., Rene. Preparations of aqueous magnetic liquids in alkaline and acidic media. IEEE transactions on magnetic. 1981, Vol. 17, pp. 1248-1249.

[6]. Wu, Wei. Sonochemical synthesis, structure and magnetic properties of air-stable Fe3O4/Au nanoparticles. Nanotechnology. 2007, Vol. 18, p. 145609.

[7]. Zhu, Aiping. Suspension of Fe3O4 nanoparticles stabilized by chitosan and o-carboxymethylchitosan. International Journal of Pharmaceutics. 2008, Vol. 350, pp. 361-368.