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研究生: 黃俊霖
Chun-Lin Huang
論文名稱: 具雙重顯影與藥物治療的多功能石墨烯量子點
Development of multifuntional graphene quantum dots as dual bioimaging and drug delivery
指導教授: 張家耀
Jia-Yaw Chang
口試委員: 王勝盟
Sheng-Meng Wang
何郡軒
Jinn-Hsuan Ho
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2014
畢業學年度: 102
語文別: 中文
論文頁數: 188
中文關鍵詞: 石墨烯石墨烯量子點核磁共振
外文關鍵詞: graphene, graphene quantum dots, MRI
相關次數: 點閱:280下載:0
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  • 第一部分:我們針對石墨烯量子點材料提出一個簡單且容易控制的製備方法,我們採用水熱合成法進行高品質與高量子產率的GQDs製備與合成,其藉由氨水來切割以氧化石墨烯為主體的前驅物進而合成出GQDs。而水熱合成法是指在特定的反應器(高壓釜)中,以水作為反應體系,藉由高溫高壓進行奈米粒子合成之方法。並可藉由調整反應溫度來控制GQDs的螢光顏色與表面胺基的量。本系統目前能夠有效控制螢光顏色於黃綠色至藍色之間。

    第二部分:藉由表面擁有羧酸和胺基的GQDs進行表面功能化,在這邊我們利用羥基丁二醯亞氨(EDC)與二甲基胺基丙基乙基碳酰胺(NHS)交聯系統作為基礎,將GQDs同時與葉酸和钆離子錯合物進行結合。葉酸為一種靶向性物質,對特定癌細胞具有特殊吸收能力,因此可作為細胞標靶之應用,而釓離子錯合物為磁性物質,可應用於核磁共振造影,最後對具有雙重顯影功能且表面已偶聯葉酸擁之folate-GdGQD進行Doxorubicin抗癌藥物附載,成功開發出同時具有癌細胞標靶、細胞螢光影像、磁振造影、藥物治療、藥物載體和追蹤藥物等六種生醫應用之多功能奈米材料,期許未來在醫學臨床上有更廣泛的應用。


      In this research, we propose a simple and facile way on preparing graphene quantum dots (GQDs) from graphene oxide via hydrothermal synthesis method. Experimentally, ammonia was applied to breakdown graphene oxide structure from which resulting high quantum yield of graphene quantum dots. In our hydrothermal system, water was directly employed and placed with graphene oxide on autoclave, then heated to give high temperature-pressure treatment. This reaction temperature can control the fluorescent color (in range green to yellow) and the number of amine site on GQDs.

      Furthermore, due to as-prepared GQDs exists a number of carboxylic acid and amine site, we use Hydroxysuccinimide amide imide (EDC) and dimethyl amino ethyl propyl carbon amide (NHS) to rendering both folic acid and gadolinium ion complexes. While folic acid addresses GQDs to be specific targeting on cancer cells, gadolinium ion complexes will feature magnetic resonance active on the nanoparticles. Finally, the successfully Dox loading completed the advantages of designed GQDs as drug delivery agent on cancer therapeutic cases. With its multi-functional ability, in the future, we optimize that the proposed GQDs can widely take apart on clinical medicine applications.

    中文摘要 I Abstract III 總目錄 IV 表目錄 XV 第一章、序論 1 1.1 前言 1 1.2 研究動機與內容 3 第二章、理論基礎與文獻回顧 4 2.1 石墨烯之基本特性 4 2.1.1 碳元素之法展與石墨烯之基本特性 4 2.1.2 石墨烯獨特的性質 6 2.1.3 石墨烯的製備 7 2.1.4 石墨烯之應用與發展 20 2.2 石墨烯量子點與量子點之特性 26 2.2.1 量子點之介紹 26 2.2.2 石墨烯量子點 29 2.2.3 石墨烯量子點的種類與區分 30 2.2.4 石墨烯量子點合成方法 32 2.2.5 石墨烯量子點之生物醫學應用 59 2.2.6 石墨烯量子點之發光機制 65 2.3 奈米材料之表面功能化 68 2.4 核磁共振影像(MRI)成像原理及影像劑的作用 73 第三章、實驗儀器與方法 75 3.1 實驗架構 75 3.2 實驗藥品 77 3.3 實驗儀器 79 3.4 實驗步驟 82 3.4.1 以強酸對石墨進行預先處理 82 3.4.2 對預先處理之石墨進行氧化形成氧化石墨烯 83 3.4.3 對氧化石墨烯進行純化 83 3.4.4 以水熱合成法製備出GQDs 83 3.4.5 以不同溫度製備螢光顏色不同之GQDs 84 3.4.6 對GQDs進行葉酸功能化修飾並純化形成folate-GQD 84 3.4.7 以DTPA作為螯合劑對folate-GQD進行Gd螯合形成folate-GdGQD 85 3.4.8 以GQDs作為藥物載體對folate-GdGQD附載抗癌藥物Doxorubicin形成folate-GdGQD/Dox 86 3.5 細胞培養 88 3.6 樣品分析 91 第四章、結果與討論 102 4.1 氧化石墨烯合成介紹 102 4.1.2 氧化石墨烯之型態與厚度 104 4.2 石墨烯量子點合成介紹 106 4.2.1 石墨烯量子點合成介紹 106 4.2.2 石墨烯量子點之最佳化條件 108 4.2.3 石墨烯量子點之型態 111 4.2.3 石墨烯量子點之發光機制 113 4.3 石墨烯量子點表面功能化合成之鑑定分析 117 4.3.1 石墨烯量子點表面功能化合成實驗介紹 117 4.3.2 石墨烯量子點表面功能化之共價偶聯法 118 4.3.3 石墨烯量子點之葉酸耦合介紹[197] 119 4.3.4 石墨烯量子點之Gd-DTPA顯影劑耦合介紹 123 4.3.5 石墨烯量子點之Gd-DTPA顯影劑耦合方法與機制 124 4.3.6 石墨烯量子點附載抗癌藥物之方法與機制 127 4.3.7 石墨烯量子點之葉酸耦合之分析鑑定 128 4.3.8 石墨烯量子點之Gd-DTPA顯影影偶合之分析鑑定 131 4.3.10 石墨烯量子點附載抗癌藥物之分析鑑定與發光機制 132 4.3.11 石墨烯量子點附載抗癌藥物之檢量線、藥物附載量與藥物釋放量 135 4.3.12 folate-GdGQD和細胞之核磁共振顯影 138 4.3.13 GQDs、folate-GdGQD和folate-GdGQD/Dox之細胞顯影 141 4.3.14 folate-GdGQD-Dox於細胞之流式細胞儀(Flow Cytometry) 148 4.3.15石墨烯量子點對細胞之毒性測試介紹 151 4.3.16 folate-GdGQD於活體動物之測試 154 第五章、結論與未來展望 158 參考文獻 160

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