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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳敏慧(Min-Huey Chen) | |
| dc.contributor.author | Karen Chang | en |
| dc.contributor.author | 張丰毓 | zh_TW |
| dc.date.accessioned | 2021-06-15T03:59:20Z | - |
| dc.date.available | 2013-10-03 | |
| dc.date.copyright | 2011-10-03 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-17 | |
| dc.identifier.citation | [1] Akinc A., and Langer R.. (2002). Measuring the pH environment of DNA delivered using nonviral vectors: implications for lysosomal trafficking. Biotechnol Bioeng 78, 503-508.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44953 | - |
| dc.description.abstract | Gene delivery has been an indispensable tool in biomedical researches. With the development of molecular biology, different materials and methods for gene delivery have long been developed and continued to be modified. We can overexpress or inhibit particular genes by delivering plasmids, antisense oligonucleotides or RNA interference (RNAi) to analyze specific gene functions. There have been two major systems for gene delivery used currently: the viral vector system and the non-viral vector system. Since the instability of viral vectors and the requirements of clinical applications, most studies still use the non-viral vectors for gene delivery.
The purpose of this study is to develop non-viral cholesterol-based nanocarriers as transfection reagent for delivering nucleic acids into cells efficiently and not affecting normal cell viability. Such platform is going to benefit the genetic manipulation of primary cells and even stem cells. A novel cationic cholesterol, 3-β-[N-(2-guanidinoethyl)carbamoyl]-cholesterol (GEC-Chol), was mixed with cholesterol to form the GEC-Chol/ Chol lipoplexes (GCC) and then incorporated with hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles to form as GCC-Fe3O4 nanocarriers. The GCC-Fe3O4 nanocarriers were transfected together with fluorescent-labeled oligonucleotides (ODN) into mouse CT-26 colon cancer cells in order to evaluate the transfection efficiency and cytotoxicity by fluorescent microscopy and further confirmed with confocal microscopy as well as flow cytometry analysis. Other cell types such as the rat acinar cells, and human embryonic stem cells were also used as primary cell and stem cell models. The results indicated that GCC-Fe3O4 nanocarriers have high physical stability with size less than 135 nm. These GCC-Fe3O4 nanocarriers also showed great transfection efficiency as well as low cytotoxicity in both serum-reducing condition and normal serum-containing medium. We also compared GCC-Fe3O4 nanocarriers with common commercialized transfection vectors and found the GCC-Fe3O4 nanocarriers had better transfection efficiency under serum condition. GCC-Fe3O4 nanocarriers not only worked well on cancer cell line, but also good for primary acinar cells and even embryonic stem cells for further tissue remodeling. Moreover, the magnetic nanoparticles may also have the potential to work as contrast agent for tracking engineered cells in vivo and can be manipulated by magnetic force. This novel developed GCC-Fe3O4 nanocarriers had the capability for high efficiency of gene delivery and molecular imaging simultaneously, and provide a better choice for future clinical applications. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T03:59:20Z (GMT). No. of bitstreams: 1 ntu-100-R98450006-1.pdf: 2034561 bytes, checksum: 6177b95c11cc516a3e13f92b35ae368a (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 誌謝......................................................i
中文摘要.................................................ii ABSTRACT................................................iii CONTENTS..................................................v LIST OF FIGURES.........................................vii LIST OF TABLES.........................................viii ABBREVIATION.............................................ix Chapter 1 Introduction....................................1 1.1 Nanotechnology........................................1 1.2 Iron oxide nanoparticles..............................2 1.3 Nanocarriers for biomedical applications..............3 1.4 Gene delivery.........................................4 1.4.1 Gene delivery by physical techniques................5 1.4.2 The non-viral chemical-based gene delivery system...6 1.4.3 Viral vectors.......................................8 1.5 Motivation and specific aims 9 1.6 Experimental Design Flowchart 10 Chapter 2 Materials and Methods 11 2.1 Materials 11 2.1.1 Chemical reagentsChemical reagents 11 2.1.2 Lipid ingredients. 11 2.1.3 Nanoparticles 12 2.1.4 Oligodeoxynucleotides 12 2.1.5 Culture cells 12 2.1.6 Experimental instruments. 12 2.2 Methods 13 2.2.1 preparation of GCC-Fe3O4 nanocarriers. 13 2.2.2 Measurement of the size and zeta potential of nanocarriers. 13 2.2.3 Cell cultures. 14 2.2.4 Deliver the GCC-Fe3O4-ODN into cells. 14 2.2.5 Analysis of the transfection efficiency and cytotoxicity. 15 2.2.6 Quantification of the transfection efficiency. 16 2.2.7 Statistical analysis. 16 Chapter 3 Results 17 3.1 Particle size and zeta potential of the lipoplexes 17 3.2 Morphology and conformation of the lipoplexes 17 3.3 Transfection efficiency of the GCC-Fe3O4 nanocarriers 18 3.4 Distribution of oligonucleotides within the CT-26 cells 19 3.5 Cytotoxicity of the GCC-Fe3O4 nanocarriers 19 3.6 Functional delivery with antisense oligodeoxynucleotides 20 3.7 Comparison of transfection efficiency with common commercialized transfection reagents 20 3.8 Delivery on primary cells and stem cells 22 Chapter 4 Discussion 23 Chapter 5 Figures and Tables 25 REFERENCE 36 | |
| dc.language.iso | en | |
| dc.subject | 超順磁氧化鐵奈米粒子 | zh_TW |
| dc.subject | 幹細胞 | zh_TW |
| dc.subject | 基因遞送 | zh_TW |
| dc.subject | 正價脂質奈米載體 | zh_TW |
| dc.subject | SPIO | en |
| dc.subject | Cationic lipid nanocarriers | en |
| dc.subject | Stem cells | en |
| dc.subject | Gene delivery | en |
| dc.title | 利用正價膽固醇為基底的奈米載體進行短鏈核苷酸遞送之效率探討 | zh_TW |
| dc.title | The Efficiency of Cationic Cholesterol-Based Nanoparticles for Oligonucleotides Delivery | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孫啟光(Chi-Kuang Sun),楊台鴻(Tai-Horng Young) | |
| dc.subject.keyword | 正價脂質奈米載體,超順磁氧化鐵奈米粒子,基因遞送,幹細胞, | zh_TW |
| dc.subject.keyword | Cationic lipid nanocarriers,SPIO,Gene delivery,Stem cells, | en |
| dc.relation.page | 44 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-18 | |
| dc.contributor.author-college | 牙醫專業學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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