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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡偉博(Wei-Bor Tsai) | |
| dc.contributor.author | Shuo-Hsiang Chou | en |
| dc.contributor.author | 周碩祥 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:36:56Z | - |
| dc.date.available | 2023-08-18 | |
| dc.date.copyright | 2020-08-28 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79017 | - |
| dc.description.abstract | 聚乙二醇修飾之脂質體已經廣泛被用來作為藥物載體應用於癌細胞治療。然而，高成本的磷脂質與其在血液中的不穩定性和聚乙二醇修飾所衍生的問題限制了其應用的範疇。藉此，我們提出一個由棕梠酸和高含量膽固醇組成的非磷脂質藥物載體，藉由羥基甜菜鹼超親水性聚合物長度和重量百分比最佳化的表面修飾條件之後，由於羥基甜菜鹼超親水性聚合物良好的抗蛋白質吸附能力，體外結果顯示有效提升在蛋白質溶液中的穩定性，進而能夠躲避巨噬細胞的辨識達到延長載體在血液中的循環時間。 進而乃至於癌細胞的治療應用，我們嘗試在修飾載體表面之高分子羥基甜菜鹼超親水性聚合物接枝上具有標靶功能可被細胞辨識的葉酸分子，包覆艾黴素作為海拉癌細胞的體外治療。從體外的毒殺試驗中，結果顯示接枝上葉酸的羥基甜菜鹼修飾高固醇載體相較羥基甜菜鹼修飾的高固醇載體具有比較好的細胞毒殺效果，而羥基甜菜鹼修飾特性也使其比相較單純施以艾黴素更能減少對一般細胞的毒性，在能不被免疫系統辨識的修飾條件下，增加藥物積累於腫瘤細胞，提升對腫瘤細胞的選擇率，此結果也與體外細胞攝取的試驗結果相呼應。藉由這些體外試驗的研究結果，顯示此由葉酸接枝的羥基甜菜鹼修飾高固醇載體具有良好乘載抗癌小分子藥物做為癌症治療的潛力。 | zh_TW |
| dc.description.abstract | Over the past few decades, liposomes composed of phospholipids have been emerging as a useful mean for drug delivery. However, the expensiveness of phospholipids and unstableness of phospholipid liposomes in the blood limit their wide applications. To surmount the challenge, we developed a non-phospholipid sterosomes decorated with a zwitterionic poly(carboxybetaine) (PCB). Superhydrophilic PCB, comparable with PEG, is expected to keep sterosomes more stable in complex media such as blood, and to imbue them with the stealth properties for escaping MPS clearance, prolonging the circulation time. In addition, targeting ligands of folic acid was conjugated to PCB-modified sterosomes, and doxorubicin was incorporated into the sterosomes for anti-cancer treatment. The results of cellular uptake indicated that the folic acid conjugated PCB-modified sterosomes triggered less the activation of macrophages and enhancement in HeLa cancer cells owing to FA decoration. Also, the results of cytotoxicity efficiency showed the decrement of HeLa in cell viability, reducing systemic toxicity of L929 fibroblast cells. All the results in vitro study mention above contributed to better selectivity of tumor cells compared to pure doxorubicin treatment, suggesting that this folic acid decorated PCB-modified sterosomes are more suitable as drug delivery carriers for anti-tumor therapy in conclusion. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:36:56Z (GMT). No. of bitstreams: 1 U0001-1808202003454200.pdf: 5770043 bytes, checksum: 60a741711748cdcb8ca2259df8fae95f (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | Content 論文口試委員審定書 I ACKNOWLEGEMENT II 摘要 III ABSTRACT IV CONTENT V LIST OF FIGURES VIII LIST OF TABLES XV CHAPTER 1 INTRODUCTION 1 1.1 Overview of anti-tumor therapy 1 1.1.1 Chemotherapy 1 1.1.2 Strategy of Nano Carriers for Cancer Therapy 5 1.2 Zwitterionic modification 9 1.2.1 Poly(carboxybetaine methacrylate) 9 1.3 Targeted therapy 11 1.4 Non-phospholipid Liposomes (Sterosomes) 13 1.5 Post-Insertion Method 16 1.6 Aims and Motivation 18 1.7 Research Framework 19 CHAPTER 2 MATERIALS AND METHODS 20 2.1 Chemicals 20 2.1.1 Synthesis of zwitterionic polymers 20 2.1.2 Preparation of liposomes 21 2.1.3 Cell culture 22 2.1.4 Cell viability 23 2.1.5 Cellular uptake 23 2.2 Experimental instruments 23 2.3 Experimental materials 24 2.4 Solution formula 25 2.5 Methods 27 2.5.1 Synthesis of PCB-based materials 27 2.5.2 Preparation of Un-modified Sterosomes 32 2.5.3 Preparation of PCB-modified Sterosomes 33 2.5.4 Characteristics of sterosomes 34 2.5.5 In vitro stability test (Protein Resistance Test) 35 2.5.6 In vitro release profile of doxorubicin 36 2.5.7 Cell culture 36 2.5.8 Cell viability 37 2.5.9 In vitro cellular uptake 38 2.5.10 Cytotoxicity test 39 2.5.11 Statistic analysis 40 CHAPTER 3 RESULTS AND DISCUSSION 41 3.1 Optimization of PCB-modified sterosomes 41 3.1.1 Gel Permeation Chromatography analysis for molecular weight 41 3.1.2 Size and Zeta potential of sterosomes formulations 42 3.1.3 Protein Resistance test 43 3.1.4 Cellular uptake of doxorubicin quantification 44 3.1.5 Cell viability of blank PCB-modified sterosomes 46 3.2 Folic acid conjugated PCB-modified sterosomes 47 3.2.1 Gel Permeation Chromatography for molecular weight 47 3.2.2 Size and Zeta potential of blank sterosomes formulations 47 3.2.3 Morphology of sterosomes under TEM 48 3.2.4 Protein Resistance test 48 3.2.5 Cytotoxicity of blank sterosomes 49 3.2.6 Characterization of DOX-loaded sterosomes formulations 50 3.2.7 UV spectra for characteristic peaks of sterosomes surface 50 3.2.8 In vitro releasing profile of Doxorubicin 51 3.2.9 Cell Killing Efficiency of DOX-loaded sterosomes 52 3.2.10 Cellular uptake of doxorubicin quantification 54 3.3 Discussion 56 CHAPTER 4 CONCLUSION 92 CHAPTER 5 FUTURE WORK 93 CHAPTER 6 REFERENCE 94 | |
| dc.language.iso | en | |
| dc.subject | 葉酸 | zh_TW |
| dc.subject | 脂質體 | zh_TW |
| dc.subject | 非磷脂載體 | zh_TW |
| dc.subject | 羥基甜菜鹼聚合物 | zh_TW |
| dc.subject | 艾黴素 | zh_TW |
| dc.subject | 抗腫瘤治療 | zh_TW |
| dc.subject | poly(carboxybetaine) | en |
| dc.subject | sterosomes | en |
| dc.subject | doxorubicin | en |
| dc.subject | folic acid | en |
| dc.subject | cancer treatment | en |
| dc.title | 利用羧酸甜菜鹼兩性離子聚合物修飾非磷脂質之高固醇載體包覆艾黴素應用於癌細胞治療 | zh_TW |
| dc.title | Development of Poly(carboxybetaine) Modified Non-phospholipid Sterosomes as Doxorubicin Carrier for Cancer Therapy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王孟菊(Meng-Jiy Wang),蔡曉雯(Shiao-Wen Tsai) | |
| dc.subject.keyword | 抗腫瘤治療,非磷脂載體,脂質體,艾黴素,葉酸,羥基甜菜鹼聚合物, | zh_TW |
| dc.subject.keyword | cancer treatment,sterosomes,doxorubicin,folic acid,poly(carboxybetaine), | en |
| dc.relation.page | 99 | |
| dc.identifier.doi | 10.6342/NTU202003915 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-18 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
| dc.date.embargo-lift | 2023-08-18 | - |
| 顯示於系所單位： | 化學工程學系 | |
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