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研究生: 劉思廷
Liu, Ssu-Ting
論文名稱: 利用金屬離子-聚電解質自組裝粒子為模板製備交聯之聚胺酸高分子中空奈米球及二氧化矽/聚胺酸高分子複合奈米殼
Preparation of Cross-Linked Polypeptide Nanocages and Silica/Polypeptide Hybrid Nanoshells Templated by Metal ion-Polyelectrolyte Assemblies
指導教授: 詹正雄
Jan, Jeng-Shiung
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
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: 85
中文關鍵詞: 中空奈米球奈米殼二氧化矽氧化還原/酸鹼應答藥物傳輸交聯聚胺基酸
外文關鍵詞: nanocage, nanoshell, silica, redox/pH responsiveness, drug delivery, cross-linked, polypeptide
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  • 本研究中,藉由金屬離子及聚電解質透過靜電作用力形成自組裝結構為模板,製備聚胺基酸交聯微胞、聚胺酸交聯中空奈米球及二氧化矽/聚胺酸複合奈米殼,此複合微胞是由聚二乙烯三胺五乙酸與胱胺高分子(poly (diethylenetriaminepentaacetic dianhydride-co-cystamine), poly(DTPA-co- cystm))、金屬離子及聚乙二醇嵌段聚賴胺酸高分子(PEG-b-poly(L-lysine), PEG-b-PLL)所組成,具有氧化還原及酸鹼雙重應答之性質。複合微胞之尺寸大小可藉由改變莫耳比例、金屬離子或是製程來調控。並以京尼平(genipin)交聯聚胺基酸複合微胞,使其在稀釋及溶液環境條件改變時,結構不易崩解。藉由控制京尼平與胺基(NH2)之比例,可得到不同交聯比例之複合微胞。聚胺基酸交聯中空奈米球可利用榖胱甘肽(glutathione, GSH)切斷雙硫鍵,移除聚二乙烯三胺五乙酸與胱胺高分子得到。另外,利用聚胺基酸交聯中空奈米球交聯複合微胞為模板沉析二氧化矽,可形成二氧化矽/聚胺基酸複合奈米殼,此材料可應用於生物醫學領域。此外,奈米複合微胞可包覆抗癌藥物阿黴素(Doxrubicin, DOX),並藉由酸鹼值的降低或雙硫鍵的斷裂進行藥物釋放,此具酸鹼及氧化還原雙重應答之複合微胞將具有潛力成為藥物載體。

    SUMMARY
    In this study, we report the preparation of cross-linked polypeptide complex micelles, cross-linked polypeptide nanocages, and silica/polypeptide hybrid nanoshells templated by metal ion-polyelectrolyte assemblies via electrostatic interaction. The complex micelles composed of poly(diethylenetriaminepentaacetic dianhydride-co-cystamine) (poly(DTPA-co-cysam)), metal ions, and PEG-b-poly (L-lysine) (PEG-b-PLL) exhibited redox/pH dual-responsive property. Their sizes can be tuned by varying the molar ratio, metal ion species, or synthesis process. These complex micelles can be cross-linked by genipin to prevent dissociation upon dilution. The cross-linked polypeptide nanocages can be prepared and used as template to form silica/polypeptide hybrid nanoshells. Furthermore, these cross-linked micelles were employed for doxorubicin (DOX) encapsulation and it was found that the DOX release can be triggered by redox/pH dual-responsiveness. These complex micelles could be promising as drug carriers.
    Keywords : nanocage, nanoshell, silica, redox/pH responsiveness, drug delivery, cross-linked, polypeptide

    摘要 I Extended Abstract II 目錄 X 表目錄 XIV 圖目錄 XV 第一章 緒論 1 1.1 前言 1 1.2 研究動機與目的 2 第二章 文獻回顧 4 2.1 聚胺基酸 4 2.1.1 胺基酸之簡介 4 2.1.2 胺基酸之聚合 5 2.2 聚電解質複合粒子 7 2.2.1 聚電解質複合粒子之簡介 7 2.2.2 聚電解質複合粒子之分類 7 2.3交聯 9 2.4 中空奈米球(hollow nanosphere) 13 2.5 生物材料與礦化作用 14 2.6 奈米載體 16 2.6.1 奈米載體簡介 16 2.6.2 奈米載體之生物訊號應答 16 第三章 實驗方法與儀器設備 23 3.1 實驗藥品 23 3.2聚乙二醇與聚賴胺酸嵌段高分子(PEG-b-PLL)和聚二乙烯三胺五乙酸與胱胺高分子poly(DTPA-co-cysam)之合成 25 3.2.1溶劑之純化 25 3.2.2 N-carboxyanhydrides (NCAs)的製備 25 3.2.3 利用一級胺對NCAs開環合成聚胺基酸 26 3.2.4 去除聚胺基酸之保護基 26 3.2.5合成聚二乙烯三胺五乙酸與胱胺嵌段共聚物poly(DTPA-co-cysam) 27 3.3複合粒子之製備 27 3.3.1聚電解質金屬複合粒子之製備 27 3.3.2以京尼平交聯複合粒子 28 3.3.3以GSH製備中空複合粒子 29 3.3.4 製備二氧化矽/聚胺基酸複合奈米殼 29 3.4藥物包覆與釋放 29 3.5特性分析與性質測試 30 3.5.1液態核磁共振儀 30 3.5.2凝膠滲透層析儀 31 3.5.3動態光散射偵測儀 32 3.5.4穿透式電子顯微鏡 35 3.5.5紅外線光譜儀 36 3.5.6圓二色光譜儀 37 3.5.7紫外光/可見光光譜儀 38 3.5.8 SAXS 39 第四章 結果與討論 41 4.1聚乙二醇與聚賴胺酸嵌段高分子(PEG-b-PLL)和聚二乙烯三胺五乙酸與胱胺高分子poly(DTPA-co-cysam)之合成與分析 41 4.1.1聚乙二醇與聚賴胺酸嵌段高分子之製備與分析 41 4.1.2聚二乙烯三胺五乙酸與胱胺高分子poly(DTPA-co-cysam)之製備與分析 43 4.2 PEG-b-PLL/poly(DTPA-co-cysam)/metal ions奈米複合粒子之製備及分析 46 4.2.1 PEG-b-PLL/poly(DTPA-co-cysam)/metal ions奈米複合粒子之製備 46 4.2.2 PEG-b-PLL/poly(DTPA-co-cysam)/Fe3+(Al3+)奈米複合粒子之分析 48 4.3 PEG-b-PLL/poly(DTPA-co-cysam)/metal ions奈米複合微胞製備交聯之中空奈米球及二氧化矽/聚胺酸複合奈米殼 55 4.3.1交聯複合粒子之製備及粒徑分析 55 4.3.2利用榖胱甘肽(GSH)製備交聯之中空奈米球及分析 60 4.3.3二氧化矽/聚胺酸複合奈米殼之製備及分析 65 4.4 PEG-b-PLL/ poly(DTPA-co-cysam)/metal ions奈米複合粒子作為藥物載體之應用 68 4.4.1製備裝載藥物之複合粒子及其分析 68 4.4.2複合粒子裝載藥物後之釋放實驗及分析 70 第五章 結論 72 第六章 參考文獻 73

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