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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 何佳安 | |
dc.contributor.author | Jyun-Wei Wen | en |
dc.contributor.author | 温竣崴 | zh_TW |
dc.date.accessioned | 2021-07-09T15:52:20Z | - |
dc.date.available | 2022-08-24 | |
dc.date.copyright | 2017-08-24 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-16 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76437 | - |
dc.description.abstract | 光動力治療是癌症常用的治療方法之一,其作用原理是透過光照來活化光敏劑,使環境中的氧氣轉換成活性氧化物質(如單線態氧分子)來毒殺癌症細胞。然而其療效會因為腫瘤微環境中的低氧濃度而降低,導致無法完全地根治癌症的病灶。本篇研究是利用在低氧環境下才具有毒殺效果的還原型前驅藥物Tirapazamine (TPZ)與光敏劑Protoporphyrin IX (PpIX)做搭配治療;藉由PpIX的作用,使腫瘤微環境中的氧氣濃度下降,藉此增強低氧還原型前驅藥物的毒殺範圍。
本篇研究的設計是將光敏劑分子修飾在具有良好生物相容性的多孔洞奈米二氧化矽球載體 (Mesoporous silica nanoparticle, MSN) 上,將TPZ裝載於其內,並在多孔奈米二氧化矽球的表面上再修飾對乳癌細胞株 MDA-MB-231具有專一性的DNA適體LXL-1,達到標靶治療的目標。 從本研究的結果中可以發現PpIX與TPZ兩種藥物在各個氧氣壓力下皆能產生協同作用,造成更有效的抗癌效果;帶有LXL-1適體修飾的MSN載體能夠專一性地被MDA-MB-231乳癌細胞吞噬,且兩種藥物裝載於載體內的毒殺效果較兩種藥物以free drug的方式更好,因此這樣複合型的治療策略是能夠有效的毒殺低氧環境下的惡性乳癌細胞。 | zh_TW |
dc.description.abstract | Photodynamic therapy (PDT) is one of common medical strategies for treating cancer. However, the hypoxic tumor microenvironment often impedes cancer cure rate and increases the likelihood of tumor recurrence. To solve this problem, we attempted to develop a new cancer treatment strategy by combining bioreductive therapy with PDT. It is anticipated that the photosensitizers PpIX will consume most of the oxygen at the tumor site, leading to the generation of singlet oxygen, and concurrently creating a low-oxygen level environment to activate the therapeutic function of bioreductive drug TPZ. Mesoporous silica nanoparticles (MSN) were chosen herein to serve as drug carriers, that were modified with photosensitizer and loaded with bioreductive drugs; in addition, a DNA aptamer LXL-1 was used to functionalize the outer surface of MSN, enabling targeted delivery of therapeutic agents to human breast cancer cell, MDA-MB-231. | en |
dc.description.provenance | Made available in DSpace on 2021-07-09T15:52:20Z (GMT). No. of bitstreams: 1 ntu-106-R03b22044-1.pdf: 5529693 bytes, checksum: 3cb2d74613a637f31f6ea6b450cf6930 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 目錄
謝誌 Ⅰ 中文摘要 Ⅱ Abstract Ⅲ 目錄 Ⅳ 圖目錄 Ⅶ 表目錄 Ⅸ 第一章 緒論 1 1-1癌症缺氧的微環境 1 1-1.1腫瘤微環境缺氧的成因與定義 1 1-1.2缺氧環境對癌症細胞的影響 2 1-1.3針對腫瘤缺氧環境的治療策略 3 1-2癌症的光動力治療 5 1-2.1光動力治療作用機制 5 1-2.2光動力治療的優劣勢與轉型契機 8 1-3 光敏劑PpIX (Protoporphyrin IX) 9 1-4低氧性還原型前驅藥物TPZ (Tirapazamine) 11 1-5人類三陰性乳癌細胞株MDA-MB-231 13 1-6藥物傳輸系統 14 1-6.1奈米載體 14 1-6.2中孔洞奈米二氧化矽球 15 1-6.3主動與被動標靶 16 1-7 LXL-1 DNA適體 17 1-8 研究動機與發想 19 第二章 實驗材料、儀器與方法 21 2-1實驗藥品與儀器 21 2-1.1 實驗藥品 21 2-1.2 實驗儀器 24 2-1.3 實驗細胞株 25 2-1.4 氣體 25 2-1.5 光源設備 25 2-1.6 氣密袋與低氧環境的操作 27 2-2 單線態氧分子的測定 28 2-2.1 PpIX在不同濃度與不同照光時間下產生單線態氧分子之變化 28 2-2.2 PpIX在不同氧氣濃度環境下產生單線態氧分子之變化 29 2-2.3 比較PpIX、PpIX-MMT2和Apt-PpIX-MMT2產生單線態氧分子之效率 29 2-3 PpIX-MMT2、Apt-PpIX-MMT2及TPZ@Apt-PpIX-MMT2的合成 30 2-4 載體的鑑定 31 2-5 定量載體內的PpIX 31 2-6 細胞培養 32 2-7 細胞內ROS測定 33 2-8 細胞存活率測試 34 2-8.1 PpIX藥物在不同氧氣濃度下的毒殺實驗 35 2-8.2 TPZ 藥物在不同氧氣濃度下的毒殺實驗 35 2-8.3 PpIX與TPZ兩種藥物的合併治療 35 2-8.4 載體毒殺實驗 36 2-8.5 Apt-PpIX-MMT2毒殺實驗 36 2-8.6 TPZ@Apt-PpIX-MMT2的毒殺實驗 36 2-9細胞吞噬Apt-PpIX-MMT2實驗 37 2-9.1 流式細胞儀分析 37 2-9.2萃取細胞內PpIX的含量 37 第三章 實驗結果與討論 39 3-1 實驗設計與目的 39 3-2 定量PpIX受到光照射後產生的單線態氧分子 42 3-3 比較PpIX於不同氧氣濃度下產生單線態氧分子之效率 43 3-4 比較不同氧氣濃度下PpIX對癌症細胞產生ROS量之差異 44 3-5 PpIX於不同氧氣濃度下毒殺癌症細胞之結果 46 3-6 TPZ藥物於不同氧氣濃度下對癌症細胞的毒殺結果 49 3-7 PpIX與TPZ兩種藥物合併的細胞毒殺結果 51 3-8 載體的特性分析及PpIX定量結果 53 3-9 Apt-PpIX-MMT2產生單線態氧分子之效率 57 3-10 載體毒殺性 58 3-11 Apt-PpIX-MMT2對MDA-MB-231細胞的毒殺性 59 3-12 PpIX與Apt-PpIX-MMT2對MDA-MB-231細胞吞噬結果 60 3-13 Apt-PpIX-MMT2對不同細胞株的吞噬結果 61 3-14 TPZ@Apt-PpIX-MMT2對乳癌細胞的毒殺結果 64 第四章 結論與未來展望 66 第五章 參考文獻 67 | |
dc.language.iso | zh-TW | |
dc.title | 探討適體標靶奈米藥物於乳癌治療的成效 | zh_TW |
dc.title | Targeting MDA-MB-231 human breast cancer cells with aptamer-functionalized nanoformulations : A synergistic combination treatment with photodynamic therapy and bioreductive therapy | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 徐士蘭,吳立真,陳平,楊佳銘,鄭建中 | |
dc.subject.keyword | 光動力治療,腫瘤缺氧,低氧性生物還原型前驅藥物,多孔洞奈米二氧化矽球載體,DNA適體, | zh_TW |
dc.subject.keyword | Photodynamic therapy,Tumor hypoxia,Bioreductive prodrug,Mesoporous silica nanoparticle,DNA aptamer, | en |
dc.relation.page | 82 | |
dc.identifier.doi | 10.6342/NTU201703762 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2017-08-17 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
dc.date.embargo-lift | 2022-08-24 | - |
顯示於系所單位: | 生化科技學系 |
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