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  • 學位論文

包覆含硼或釓的磁性鈷奈米碳球作為中子捕獲抗癌試劑

Boron or Gadolinium Filled Magnetic Carbon nanoparticles for Thermal Neutron capture and Anticancer reagents

指導教授 : 黃國柱
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摘要


根據文獻從1936年至今已經有70年之久的歷史,中子捕獲治療乃是將元素10B以及157Gd的藥物,注射到人體內,利用腫瘤細胞對藥物具有高度的吸收性質或是以修飾專一選擇性的官能基或抗體,使得藥物得以在腫瘤細胞上產生效果,而因為10B、157Gd具有高中子捕捉截面的緣故,在照射中子束後,反應經由一核反應放射出高能量的α以及r射線來殺死癌細胞,目前以硼的藥物較具為療效,但目前文獻所提供的資料,說明目前中子捕獲治療所遭遇到的兩個問題,第一個為藥物選擇性在癌細胞上的問題,第二為劑量能夠殺死一個癌細胞的問題。根據已知文獻,目前還沒有利用奈米碳微粒當作載體,在碳微粒內部包覆高中子捕獲能力的元素,如:10B及157Gd等元素,且157Gd可以作為MRI的對比試劑,因此本篇論文當中分為兩部分來探討我們的研究。 第一部分我們利用直流電弧電漿的製備方式,製備出具有高純度80%含硼與鈷以及釓與鈷的磁性奈米碳微粒,結果當中我們也證明成功的製備出包含硼與鈷以及釓與鈷的磁性奈米碳微粒,且以利用Polyacylic acid水溶性官能機修飾在碳微粒表面,接上對腫瘤細胞上Folate receptor具有專一辨識能力的葉酸,以達到水溶性及專一選擇性藥物的攜帶。 第二部分則是著重於Hela細胞的的培養、細胞活性測試、藥物毒性測試以及中子照射細胞含硼與鈷以及釓與鈷的磁性奈米碳微粒。在藥物劑量部分,我們利用穿透式電子顯微鏡中的電子能量損失光譜EELS Mapping以及感應耦合電漿原子發射光譜分析儀ICP-AES作為硼鈷以及釓鈷奈米碳球的比例,且經由計算發現硼鈷以及釓鈷奈米碳球使用於照射中子的劑量約為22.4 μg 10B / g cell以及17.818 * 105 μg Gd /g cell,硼劑量大約等於文獻上所提的所需25~30 μg 10B / g cell,但在含有硼鈷以及釓鈷之奈米碳球加入細胞照射中子後,有明顯的效果顯示硼鈷奈米碳球使HeLa細胞致死率59 + 5 %而釓鈷奈米碳球則為75 + 5 %,這也初步顯示出我們的奈米碳球是可以當做載體使藥物送至腫瘤細胞並發揮作用。

並列摘要


In 1936, Gordon L. Locher formulated his binary concept of treating cancer. In particular, there exist the possibilities of introducing small quantities of strong neutron absorbers into the region where it is desired to liberate ionization energy (a simple illustration would be the injection of a soluble, nontoxic compound of boron, gadolinium, followed by bombardment with thermal neutron).The efficacy is dependent on the cross-section of neutron capture element (1 barn = 10-24cm2). The 10B isotope has a neutron capture cross-section of 3838 barn and the 157Gd has a neutron capture cross-section of 255000barn. There are two important factors that it can’t be solved in trail now: (1) target delivery of drugs to tumor sites; (2) sufficient high dose at tumor sites as predicted by theoretical calculation.In the literature, no one has ever reported the use of carbon nanoparticles to carry a large quantity of 10B or 157Gd element for cancer therapy.The thesis was divided into two parts: (a)First one We prepare boron or gadolinium filled magnetic carbon nanoparticle by DC arc discharge method. Carbon nanoparticles surface-grafted with polyacrylic acids were dissolved in H2O, and then further modified with folic acid. The folic acid moiety can drive carbon nanoparticles to the folate receptor sites on the surface of tumor cells. Second one is to focus on cell culture、MTT assay、toxicity assay and neutron irradiate cell with or without HeLa cell. We use many spectroscopic methods such as, (TEM、SEM、XRD、EELS mapping and ICP-AES…..etc) to determine the presence and the quantity of boron or Gadolinium in carbon nanoparticle. After carrying out toxicity assay, we evaluate the dose of 10B and 157Gd of 22.4 μg 10B / g cell and 17.818 μg 157Gd / g cell. It’s close to the cancer dose 25~30 μg 10B / g cell predicted in the literature. Our experimental results show that the 10B and 157Gd containing carbon nanoparticles are very effective, upon irradiation of neutron, in killing cells with high death fraction of 59 + 5 % and 75 + 5 % , respectively, for 10B and 157Gd containing carbon nanoparticles. Our experimental results are proofs of the concept that carbon nanoparticle can be used as neutron capture reagent.

參考文獻


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