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研究生:鄭宇勝
研究生(外文):Yu-ShengCheng
論文名稱:雙股DNA修飾之金奈米棒作為具選擇性的藥物運輸平台
論文名稱(外文):DNA-conjugated gold nanorods as a selective drug delivery platform
指導教授:葉晨聖
指導教授(外文):Chen-Sheng Yeh
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學系碩博士班
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:76
中文關鍵詞:近紅外光金奈米棒去氧核醣核酸奈米載體
外文關鍵詞:near-infraredgold nanorodDNAnanocarrier
相關次數:
  • 被引用被引用:1
  • 點閱點閱:188
  • 評分評分:
  • 下載下載:26
  • 收藏至我的研究室書目清單書目收藏:0
在本篇研究中,我們設計新的負電型奈米載體結構:藉著將雙股去氧核醣核酸(Deoxyribonucleic acid,DNA)修飾在金奈米棒表面作為攜帶雙重抗癌藥物鉑的前驅藥物(Pt(IV)-prodrug)和艾黴素(Doxorubicin,Dox)的載體,其中Pt(IV)-prodrug經由化學共價鍵接在雙股DNA的尾端,而Dox則是利用非共價鍵嵌入於雙股DNA的鹼基對間。由於此奈米載體與細胞膜表面皆帶負電,因此在靜電排斥力的作用之下,攜帶藥物的奈米載體並不會被正常細胞攝入,因而不會對正常細胞造成傷害,然而當以近紅外光雷射照射時,具高效率光熱轉換性質的金奈米棒便可以使表面對熱敏感的的雙股DNA受熱使兩股序列解旋,釋放出來Pt(IV)-prodrug與Dox分子在被癌細胞攝入後即可達到治療的效果。此一同時攜帶雙重抗癌藥物的奈米載體,經由釋放出來的Pt(IV)-prodrug和Dox分子間的協同作用(synergism)之下能夠大幅的提升對於癌細胞的毒殺效果。這些結果顯示雙股DNA修飾之金奈米棒能夠利用材料不會被細胞攝入的性質並搭配近紅外光雷射對於藥物的控制釋放,以減少化療藥物對於正常細胞產生的副作用而達到具選擇性的治療效果,並且在雙重抗癌藥物的作用之下能夠顯著的提升癌細胞的治療效率。

In the present study, we conjugated the thermosensitive double helices DNA on gold nanorods to demonstrate codelivery of drug and prodrug. The antineoplastic drugs Pt(IV)-prodrug and doxorubicin (Dox) were loaded to the double-stranded DNA by covalent bonding and non-covalent intercalation respectively. Since both the nanoplatform and the surface of the cell are negatively charged, the nanoplatform will not be uptaken by cells. Whereas upon the irradiation of near-infrared laser at the target site, such as malignant cells, the double-stranded DNA dehybridize to release Pt(IV)-prodrug and doxorubicin due to the photothermal conversion of gold nanorods. This codelivery of Pt(IV)-prodrug and doxorubicin with single nanocarriers promise both the drugs available at cell level. Hence, the cytotoxicity to A549 and MCF-7 cancer cell lines increase dramatically. These results indicate that the Pt(IV)/Dox-dsDNA-Au NRs nanoplatform can release the drug at target site to evade the damages to normal cells and offer high therapeutic efficiency via synergism.
第一章 緒論............1
1-1奈米材料簡介............1
1-2金奈米棒介紹與應用............5
1-2.1金奈米棒之光學性質............5
1-2.2金奈米棒之合成............9
1-2.3金奈米棒之表面修飾............12
1-2.4金奈米棒之應用............17
第二章 實驗藥品與儀器設備............24
2-1實驗藥品............24
2-1.1合成Pt(IV)/Dox-dsDNA-Au NRs奈米材料及實驗相關之化學藥品............24
2-1.2細胞實驗所需之化學藥品............26
2-2儀器設備............27
第三章修飾雙股DNA之金奈米棒攜帶雙重抗癌藥物作為具選擇性的藥物運輸平台於近紅外光驅動藥物釋放之應用............29
3-1研究動機與目的............29
3-2實驗步驟............31
3-2.1製備金奈米棒(Au Nanorods,Au NRs)............31
3-2.2製備表面修飾單股DNA之金奈米棒(ssDNA-Au NRs)............32
3-2.3製備表面修飾雙股DNA之金奈米棒 (dsDNA-Au NRs)............33
3-2.4 製備接有抗癌藥物Pt(IV)-prodrug之雙股DNA金奈米棒(Pt(IV)-dsDNA-Au NRs)............34
3-2.5製備同時攜帶P(IV)-prodrug及Doxorubicin兩種抗癌藥物之雙股DNA金奈米棒(Pt(IV)/Dox-dsDNA-Au NRs)............35
3-2.6定量金奈米棒上之雙股DNA............35
3-2.7抗癌藥物Pt(IV)-prodrug與Dox於dsDNA-Au NRs之穩定性測試............36
3-2.8 Pt(IV)/Dox-dsDNA-Au NRs照射連續波二極體808 nm近紅外雷射進行藥物釋放............37
3-2.9細胞培養與細胞內吞作用之觀察............37
3-2.10近紅外光驅動釋放奈米材料之抗癌藥物對癌細胞治療效果與顯影之觀察............38
3-2.11細胞毒性測試(MTT assay)............39
3-3實驗結果與討論............41
3-3.1 CTAB-AuNRs材料鑑定:UV-vis、TEM、Zetapotential、FT-IR............41
3-3.2 ssDNA-AuNRs材料鑑定:UV-vis、TEM、Zetapotential、FT-IR............43
3-3.3 dsDNA-AuNRs材料鑑定:UV-vis、TEM、Zetapotential、FL............45
3-3.4 dsDNA-Au NRs作為藥物載體攜帶Pt(IV)-prodrug與Doxrubicin............46
3-3.5 Dox分子嵌入雙股DNA金奈米棒之螢光行為............49
3-3.6材料進行細胞毒性測試............50
3-3.7 Pt(IV)-prodrug與Doxrubicin於雙股DNA金奈米棒載體上之穩定性測試.............51
3-3.8以近紅外光雷射作為藥物控制釋放............53
3-3.9利用高解析度光學顯微鏡及流式細胞儀觀察Dox釋放行為............56
3-3.10細胞攝入行為之觀察............59
3-3.11近紅外光驅動藥物釋放之化學治療效果............60
第四章結論............67
參考文獻............68

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