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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 林?輝 | |
| dc.contributor.author | Hui-Chen Hsieh | en |
| dc.contributor.author | 謝慧真 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:33:37Z | - |
| dc.date.available | 2020-09-02 | |
| dc.date.copyright | 2015-09-02 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-12 | |
| dc.identifier.citation | [1] H. Drakesmith and A. Prentice, 'Viral infection and iron metabolism,' Nature Reviews Microbiology, vol. 6, pp. 541-552, Jul 2008.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52911 | - |
| dc.description.abstract | 超順磁性奈米粒子(SPIO)具有生物相容性及易被生物體降解的特性，而被廣泛應用在生物研究及醫學臨床上，如顯影劑、藥物載體、熱治療藥物及蛋白質分離性磁珠。聚乙二醇 (PEG) 是通過FDA標準的其中一種高分子聚合物，經由PEG包覆後的SPIO具良好均勻分散在水溶液的特性和生物相容。PEG包覆除了提供良好的分散性之外還提供具有容易修飾的末端基，末端基常被使用在嫁接各種藥物或是抗體並應用在抗癌藥物的研究。但近年來報導指出SPIO奈米粒子會造成細胞的毒性，研究其原因如下：SPIO具高的體表面積比例，且具有過渡金屬特性，易高濃度累積在細胞內。但對於SPIO-PEG造成細胞死亡的機制及途徑皆尚不清晰，因此本研究對於SPIO-PEG造成細胞死亡的機制及途徑探討共分為二部分：第一部分探討SPIO-PEG導致乳癌細胞 (MCF7) 死亡之原因，發現SPIO-PEG造成乳癌細胞死亡的原因是由於累積在粒線體中，進而引發大量的ROS，除了破壞粒線體，也誘發乳癌細胞走向apoptosis的途徑。第二部分在材料上探討SPIO-PEG micelles造成累積在粒線體的原因，發現SPIO-PEG會經由環境pH值改變而降解PEG後，nanoparticles 最後到達粒線體進而SPIO聚集成團狀，導致誘發惡性乳癌細胞 (MDA-MB-231) 走向細胞壞死(necrosis) 和細胞凋亡(apoptosis)。由以上結果指出SPIO-PEG會導致乳癌細胞經由累積在粒線體而走向細胞凋亡 (MDA-MB-231 and MCF7), 和細胞壞死 (MDA-MB-231)，但比較不會影響其他的細胞 (3T3 and RAW264.7)。 | zh_TW |
| dc.description.abstract | Superparamagnetic nanoparticles are common using in medical application such as contrast agent, hyperthermia and magnetic carrier due to biodegradability and biocompatibility. Polyethylene glycol (PEG) are FDA approved polymer, and well development coated with nanoparticles since have hydrophilic property, decrease immune effects and easy modification of end group. However, there are more reported to indicate SPIO nanoparticles toxicity in cell and animals study. The results debated in the SPIO research due to various experiments. The mechanism of SPIO toxicity may be result from nanoparticles have high ratio of surface to volume, large amount resident, and transition metal property. Although, various cells have different tolerance in nanoparticles concentration; nanoparticles still impact cells and result in cancer cell death by necrosis or apoptosis. In this study to divide into two parts, one is to understanding the role of nanoparticles to result in breast cancer death, the other is to explore drive force of nanoparticles form architecture to accumulation in mitochondria. SPIO were synthesis by co-precipitation which coating with oleic acid in procedure to avoid oxide on SPIO and replacement PEG in late stage for hydrophilic property. 3T3, RAW264.7, MCF7 and MDA-MB-231 were used to explore cell tolerance, tracked SPIO and residence. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:33:37Z (GMT). No. of bitstreams: 1 ntu-104-D93548008-1.pdf: 2177780 bytes, checksum: b5f1a2cf4258ffd1c0c411604c002306 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 致謝 i ABBREVIATIONS iii 中文摘要 iv ABSTRACT v CONTENTS vi LIST OF FIGURES ix Chapter 1 Introduction 1 Chapter 2 ROS-induced toxicity: exposure of 3T3, RAW264.7, and MCF7 cells to superparamagnetic iron oxide nanoparticles results in cell death by mitochondria dependent apoptosis .5 2.1 Introduction 5 2.2 Materials and Methods 7 2.2.1 The synthesis of SPIO nanoparticles 7 2.2.2 The preparation of SPIO-PEG 8 2.2.3 The analysis of particle size, morphology and crystal structure of synthesized SPIO-PEG by TEM 9 2.2.4 X-ray diffraction analysis 9 2.2.5 The analysis of particle size distribution 9 2.2.6 Cytotoxicity evaluation 9 2.2.7 Mitochondria activity 10 2.2.8 Measurement of ROS 10 2.2.9 The TEM preparation of the SPIO-PEG in cell endosome and mitochondria 11 2.2.10 The Annexin V and PI assay for cell apoptosis by flowcytometry 11 2.2.11 Statistics 11 2.3 Results 12 2.3.1 Materials characterization of SPIO-PEG nanoparticles 12 2.3.2 The evaluation of cytotoxicity and mitochondrial activity 14 2.3.3 The SPIO-PEG nanoparticles in endosome/lysosome and mitochondria 16 2.3.4 The ROS measurement of the cells treated with SPIO-PEG nanoparticles 20 2.3.5 Relating of ROS-induced toxicity 22 2.3.6 Apoptosis measurement of the three kinds of test cells 24 2.4 Discussion. 26 2.4.1 Particle size 26 2.4.2 Mitochondria 26 2.4.3 ROS…. 28 2.4.4 TEM……. 29 2.4.5 The potential mechanism for NP resided in mitochondria 29 2.5 Conclusion 31 Chapter 3 Breast cancer cell apoptosis through pH-sensitive degradable SPIO-PEG micelles in Mitochondria 32 3.1 Introduction 32 3.2 Materials and Methods 34 3.2.1 The preparation of SPIO-PEG 34 3.2.2 Characteristic of SPIO-PEG 35 3.2.3 Cytotoxicity evaluation 36 3.2.4 Cell viability evaluation 37 3.2.5 The TEM preparation of the SPIO-PEG in cell 37 3.2.6 Zeta and Size measure 37 3.2.7 Intracellular of Fe level 38 3.2.8 Measurement of intracellular ROS 38 3.2.9 TUNEL assay 38 3.2.10 Statistics 39 3.3 Results and Discussion 39 3.3.1 Characteristic of SPIO-PEG 39 3.3.2 Cytotoxicity and viability 43 3.3.3 SPIO-PEG location: TEM 46 3.3.4 Zeta and Size 47 3.3.5 Intracellular of Fe level: ICP 49 3.3.6 Measurement of intracellular ROS 50 3.3.7 TUNEL assay 52 3.4 Conclusion 53 REFERENCES 55 | |
| dc.language.iso | en | |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | SPIO | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 乳癌細胞 | zh_TW |
| dc.subject | SPIO | en |
| dc.subject | Mitochondria | en |
| dc.subject | Apoptosis | en |
| dc.subject | Breast cancer | en |
| dc.title | 超順磁性奈米粒子於乳癌細胞死亡機制之研究 | zh_TW |
| dc.title | A Study of SPIO-PEG Nanoparticles on the Mechanism of Breast Cancer Cell Apoptosis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 陳中明,謝文元 | |
| dc.contributor.oralexamcommittee | 孫瑞昇,郭士民,張淑真 | |
| dc.subject.keyword | SPIO,粒線體,細胞凋亡,乳癌細胞, | zh_TW |
| dc.subject.keyword | SPIO,Mitochondria,Apoptosis,Breast cancer, | en |
| dc.relation.page | 59 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-13 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| Appears in Collections: | 醫學工程學研究所 | |
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