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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡偉博(Wei-Bor Tsai) | |
dc.contributor.author | Ning-Chu Chang | en |
dc.contributor.author | 張甯筑 | zh_TW |
dc.date.accessioned | 2021-06-17T06:25:41Z | - |
dc.date.available | 2023-08-27 | |
dc.date.copyright | 2018-08-27 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-08-17 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72146 | - |
dc.description.abstract | 聚乙二醇修飾之脂質體已被用來作為穩定脂質體,由於聚乙二醇作為修飾脂質體的材料仍有以下缺點:PEG同時具有疏水及親水性,其疏水性會降低liposome在水相的極性,進而使得其穩定,減少藥物由微脂體內漏出;PEG不利於抗體連結於微脂體上,而且會干擾抗體-抗原的結合,減少細胞攝取。在傳輸基因和核酸有PEG dilemma,也會減少細胞攝取。如果沒有足夠的膽固醇,PEG-磷脂質傾向於相分離並聚集。以Chol-PEG修飾的脂質體的循環持久性比PEG-phospholipids還短。根據推測,因為Chol-PEG中的膽固醇使PEG鏈位於脂雙層中更深處,被認為是Chol-PEG傾向於干擾脂雙層的原因,導致包載藥物相對快速釋放,尤其是在高Chol-PEG密度下。而兩性離子羥基甜菜鹼聚合物修飾之脂質體已被證實同樣具有良好的穩定性效果,且對PH值變化具有反應,PCB修飾脂質體在酸性條件下的持續釋放可能是因為PCB在酸性條件下羧酸基的質子化,而腫瘤環境已被證實比一般組織要來的酸。
我們的研究結果顯示,經羥基甜菜鹼聚合物修飾之脂質體擁有良好的穩定性,接上葉酸後具有標靶的效果,可以增加藥物積累於腫瘤細胞,使細胞死亡,這些體外抗腫瘤結果顯示,此研究可以進一步做體內研究。 | zh_TW |
dc.description.abstract | Although PEGylated liposomes are a promising application for anti-tumor therapy due to achieving a longer circulation time for the delivery drugs to a tumor via the enhanced permeability and retention (EPR) effect, PEG interferes with antibody-antigen binding, reducing cellular uptake. In this study, we developed a targeted zwitterionic poly(carboxybetaine) (PCB) modified liposomes for anti-tumor therapy in vitro study. PCB raises the polarity of the aqueous phase and enhance the hydration of lipid polar group regions, thus avoiding those membrane-destabilizing issues of PEG. The liposomes were encapsulated with doxorubicin (DOX), which is widely used clinically because of its broad spectrum anti-tumor activity, such as breast cancer and ovarian cancer. Phospholipid DPPE and Cholesterol was modified with PCB. Both modified lipid were used to prepare liposomes. In addition, DPPE-PCB was conjugated with folic acid, which further improved the active targeting to tumors and minimized the nonspecific uptake by normal cells. The FA-PCB-DPPE liposomes were much stable and showed higher cellular uptake to murine breast carcinoma 4T1 cells which overexpressing the folate receptor but not to L929 fibroblast cells. The liposomes composed of DSPC, CHOL-PCB, and DPPE-PCB also achieved high stability; however, due to its prolonged retention, with the lack of targeted effect to cells, the drug could not reach the cells effectively. The results of different liposomes in cell viability were consistent with the results from cellular uptake. PCB-modified liposomes provided slower drug leakage and higher stability than PEGylated liposomes. Furthermore, The FA-PCB-DPPE liposomes loaded with DOX exhibited slowly drug leakage rates, which was similar to DPPE-PCB and DSPE-PEG liposomes. These results indicated that targeted PCB-modified liposomes have great potential as a drug delivery system in anti-tumor therapy. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T06:25:41Z (GMT). No. of bitstreams: 1 ntu-107-R05524045-1.pdf: 3530947 bytes, checksum: bf9b9dcdce67e4e4fc595a0b4ec71270 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 致謝 I
摘要 II ABSTRACT III CONTENT V LIST OF FIGURES VIII LIST OF TABLES XI CHAPTER 1 INTRODUCTION 1 1.1 Anti-tumor therapy 1 1.1.1 Overview of anti-tumor therapy 1 1.1.2 Chemotherapy 2 1.1.3 Targeted therapy 5 1.2 Liposomes 8 1.2.1 Overview of liposomes 8 1.2.2 Categories of liposomes 10 1.2.2.1 Conventional liposomes 10 1.2.2.2 PEGylated liposomes 11 1.2.2.3 Targeted liposomes 12 1.2.2.4 Theranostic liposome 13 1.2.3 Surface modification of liposomes 14 1.3 Motive and aim 16 1.4 Research frame work 18 CHAPTER 2 MATERIALS AND METHODS 19 2.1 Chemicals 19 2.1.1 Zwitterionic polymers 19 2.1.2 Preparation of liposomes 20 2.1.3 Cell culture 21 2.1.4 Cell viability 22 2.1.5 Cellular uptake 22 2.2 Experimental instrument and materials 22 2.2.1 Experimental instrument 22 2.2.2 Experimental materials 24 2.3 Solution formula 25 2.4 Methods 27 2.4.1 Synthesis of PCB-based materials 27 2.4.1.1 Synthesis of 2-tert-butoxy-N-(2-(methacryloyloxy)ethyl)-N,N-dimethyl-2-oxoethanamonium (CB-tBu Monomer) 27 2.4.1.2 Synthesis of NHS-PCB-tBu via RAFT Polymerization 28 2.4.1.3 Synthesis of DPPE-PCB Conjugat 29 2.4.1.4 Synthesis of FA-PCB-DPPE via click chemistry 30 2.4.1.5 Synthesis of CHOL-PCB Conjugate 32 2.4.2 Preparation of Liposomes 34 2.4.3 Cell culture 35 2.4.4 Characteristics of liposomes 37 2.4.5 In vitro release profile of doxorubicin (DOX) 38 2.4.6 In vitro stability test 38 2.4.7 Cell viability 38 2.4.8 In vitro cellular uptake 39 2.4.9 Statistic analysis 40 CHAPTER 3 THE PROPERTY AND CHARACTERIZATION OF POLY(CARBOXYBETAINE) PCB-MODIFIED LIPOSOME 41 3.1 The NMR of CB-tBu, PCB-tBu, DPPE-PCB, FA-PCB-DPPE and CHOL-PCB 41 3.2 Characterization of poly(carboxybetaine) PCB-modified Liposome 44 3.3 Cell viability of liposomes 45 3.3.1 MTT assay 45 3.3.2 Live/Dead assay 46 3.4 In vitro stability test 47 3.5 In vitro release profile of doxorubicin (DOX) 47 3.6 In vitro cellular uptake of liposomes 48 3.6.1 CLSM 48 3.7 Discussion 49 CHAPTER 4 CONCLUSION AND FUTURE WORK 71 REFERENCE 72 APPENDIX 76 | |
dc.language.iso | en | |
dc.title | 兩性離子羥基甜菜鹼聚合物修飾之脂質體的體外抗腫瘤研究 | zh_TW |
dc.title | Zwitterionic Poly(carboxybetaine) Modified Liposomes for Anti-Tumor Therapy: An In Vitro Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 游佳欣(Jiashing Yu),王潔(Jane Wang) | |
dc.subject.keyword | 抗腫瘤治療,脂質體,兩性離子,羥基甜菜鹼聚合物, | zh_TW |
dc.subject.keyword | Anti-Tumor Therapy,Liposome,poly(carboxybetaine) (PCB),Targeted drug delivery system, | en |
dc.relation.page | 76 | |
dc.identifier.doi | 10.6342/NTU201803733 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-08-17 | |
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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