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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王勝仕(Sheng-Shih Wang) | |
dc.contributor.author | Su-Chun How | en |
dc.contributor.author | 侯素君 | zh_TW |
dc.date.accessioned | 2021-06-16T06:40:28Z | - |
dc.date.available | 2019-08-01 | |
dc.date.copyright | 2014-08-01 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-29 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57288 | - |
dc.description.abstract | 親疏兩親性之以多肽為基礎共聚物經自組裝形成微胞。因其具有可包覆大量載
物、穩定性佳,且具有良好之生物相容性等特性,因此近年來被廣泛的研究做為 生物活性劑或藥物之載體。 吾人擬以醣基修飾之共多肽poly(L-glutamic acid)-b-polyglycine-glactobionolactone(LGG)自組裝形成微胞作為吾人的系統載體,進行抗癌藥物阿黴素(doxorubicin)的包覆。吾人利用微胞內外之pH值梯度,外加超音波震盪使阿黴素擴散至微胞內部,達到約40wt%高程度的藥物包覆率(encapsulation efficiency,%)。 吾人更進一步進行細胞實驗,以hepG2 肝癌細胞作為模型,觀察醣基修飾之共多肽 poly(L-glutamic acid)-b-polyglycine-g-lactobionolactone(LGG)自組裝形成之微胞之細胞毒性,發現即使是在高濃度的情況下亦無法對細胞產生毒性。而LGG進行阿黴素之藥物包覆後,與未經醣基修飾之共多肽poly(L-glutamic acid)-b-polyglycine(GG)自組裝之微胞包覆阿黴素及未經包覆之阿黴素相比,發現在相同之阿黴素劑量下其對HepG2 肝癌細胞之致死率相若。又由於醣基對於HepG2 肝癌細胞具有靶向性,因此在低劑量之阿黴素環境下,LGG包覆阿黴素,與相同劑量之GG包覆阿黴素及未經包覆之阿黴素相比,其治療效果更加之明顯。 吾人在此研究中, 不但以MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide) 測試細胞存活率,也以流式細胞儀進一步進行細胞凋亡路徑之分析與細胞吞噬量之量測。 | zh_TW |
dc.description.abstract | Amphiphilic polypeptide-based copolymers self-assemble to form micelles.Because the micelles can encapsulate large quantities of cargoes, and have good stability and biocompatibility, they have been widely studied for use as bioactive agents or drugs in recent years.
We used saccharide-modified copolypeptides, poly (L-glutamic acid)-bpolyglycine-g-lactobionolactone (LGG), which self-assembled to form micelles as our carrier for encapsulating an anticancer drug doxorubicin (DOX). We employed the pH gradient between inside and outside of the micelles and sonication to diffuse DOX to the interior of the micelles, and to achieve a high level of the drug encapsulation efficiency(%) of about 40wt%. Cell culture experiments were conducted by using HepG2 liver cancer cells as our model. Toxicity of micelles formed from self-assembling of saccharide-modified copolypeptide, poly(L-Glutamic acid)-b-polyglycine-g-lacto-bionolactone (LGG) was studied. It was discovered that LGG is non-toxic to the cells even in a high-dose DOX condition. When DOX-loaded LGG micelles were compared with DOX-loaded poly(L-glutamic acid)-b-polyglycine (GG) micelles and free DOX, it was observed that they have comparable cytotoxicities under the same DOX-dose condition. Givem that saccharide is a model targeted ligand to HepG2 liver cancer cells,DOX-loaded LGG micelles have more apparent therapeutic effect than DOX-loaded GG and free-DOX at the same low DOX-dose condition. In this work, apart from using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to examine the viability of the cells, flow cytometry was utilized to analyze the apoptosis pathway of cells and the cellular uptake. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T06:40:28Z (GMT). No. of bitstreams: 1 ntu-103-R01524041-1.pdf: 5677490 bytes, checksum: fa96f48d9cae7aa8239f058441c27607 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 v 英文摘要 vi 目 錄 vii 圖目錄 ix 第一章 緒論 1 1.1. 研究動機 1 1.2. 章節概述 2 第二章 文獻回顧 4 2.1 共多肽微胞(Copolypeptide micelle) 4 2.2 靶向藥物輸送系統(Targeted drug delivery system) 5 2.3 載體醣基化(Glycosylated carriers) 6 2.4 凝集素受體(Lectin aeceptors) 7 2.5 肝臟疾病 11 2.5.1. B型肝炎 15 2.5.2. 肝臟纖維化(Liver fibrosis) 17 2.5.3. 肝癌 17 2.6. 肝臟疾病臨床上之治療及挑戰 21 2.6.1. B型肝炎治療 21 2.6.2. 肝纖維化治療 22 2.6.3. 肝癌治療 23 2.6.4. 去唾液酸醣蛋白受體 (Asialoglycoprotein receptor) 26 2.6.4. 乳糖酸(Lactobionic acid) 28 2.7. 蔥環類(Anthracyclines)抗癌藥物-阿黴素(Doxorubicin) 32 2.8. 實驗檢測原理介紹 36 2.8.1. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) 還原測試法 36 2.8.2. 流式細胞技術 (flow cytometry) 42 第三章 實驗藥品、儀器與步驟 46 3.1. 實驗藥品 46 3.2. 實驗儀器 47 3.3. 實驗流程 48 3.3.1. GG/LGG微胞(micelle)製備 48 3.3.2. GG/LGG包覆阿黴素(doxorubicin(DOX)) 48 3.3.3. 細胞培養 49 3.3.4. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) 還原分析法(MTT reduction assay) 49 3.3.5. 細胞凋亡分析 50 3.3.6. 細胞吞噬阿黴素之分析實驗 51 第四章 實驗結果與討論 52 4.1. LGG載體對HepG2肝癌細胞之毒殺性 52 4.2. LGG載體包覆阿黴素對HepG2肝癌細胞之毒殺性 53 4.3. 以雙染劑染色並以流式細胞儀分析細胞凋亡 54 4.4. 以流式細胞儀分析細胞吞噬阿黴素藥物量 62 第五章 結論與建議 66 參考文獻 69 | |
dc.language.iso | zh-TW | |
dc.title | 利用接枝半乳糖基之聚(L-谷氨酸)-聚甘氨酸微胞包覆阿黴素作為具潛力之肝癌治療藥劑 | zh_TW |
dc.title | Using Doxorubicin-loaded poly(L-glutamic acid)-b-polyglycine-g-lactobionolactone micelles as potential therapeutic agents for Hepatocellular carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 詹正雄(Jeng-Shiung Jan),王孟菊(Meng-Jiy Wang),林達顯(Ta-Hsien Lin),邱文英(Wen-Yen Chiu),胡朝榮(Chaur-Jong Hu) | |
dc.subject.keyword | 醣基修飾共多?,自組裝微胞,細胞凋亡, | zh_TW |
dc.subject.keyword | saccharide -modified copolypeptides,self-assembleed micelle,cell apoptosis, | en |
dc.relation.page | 81 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-07-30 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
顯示於系所單位: | 化學工程學系 |
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