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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40221
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dc.contributor.advisor牟中原(Chung-Yuan Mou)
dc.contributor.authorWei Chenen
dc.contributor.author陳緯zh_TW
dc.date.accessioned2021-06-14T16:42:53Z-
dc.date.available2016-08-16
dc.date.copyright2011-08-16
dc.date.issued2011
dc.date.submitted2011-08-13
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40221-
dc.description.abstract近年來磁共振造影已成為醫療診斷上重要的工具之一,其中磁共振顯影劑方面的研究更是此領域相當重要的一部分,隨著奈米科技臻於成熟,因此開發個人化的奈米粒子顯影劑,儼然已成為科學家們所共同努力的目標。本研究主要分為兩部分,第一部分為利用熱分解方法合成錳鐵雙金屬氧化物奈米粒子,透過穿透式電子顯微鏡、超導量子干涉儀、感應耦合電漿質譜儀及X光粉末繞射儀鑑定其組成及結構,為了進一步於生物上之應用,於此奈米粒子表面包覆一層二氧化矽殼層,並可同時包覆螢光劑於此殼層內達成雙功能(磁性和螢光)的奈米粒子。活體之應用為將此奈米粒子以尾靜脈方式送入大鼠體內,以進行磁共振顯影的實驗,結果顯示,於腦內之海馬迴、腦垂體、小腦、下顎腺以及腎臟皆有明顯之顯影效果,其原因也詳細地探討。
  第二部分為利用四氧化三鐵包附上具有中孔洞二氧化矽的奈米粒子,同時可將螢光劑鑲嵌於此二氧化矽的結構中以合成三功能(磁性、螢光和中孔洞)之奈米粒子。細胞實驗測試中,此奈米粒子具有高度的生物相容性且證實可進入細胞,利用流式細胞儀和磁共振顯影可得到高度的標的效率和明顯之影像對比效果。以上結果證實此多功能奈米粒子於細胞標的以及細胞追蹤上極具潛力。
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dc.description.abstractIn recent years, magnetic resonance imaging (MRI) plays an important role in bioimaging. Therefore, magnetic nanoparticles have attracted much attention as MRI contrast agents. Herein, we report a core shell bifunctional nanoparticle, MIO@SiO2-RITC (core: manganese iron oxide, MIO; shell: amorphous silica conjugated with RITC) with both fluorescent and magnetic properties for MR imaging. By tuning iron to manganese ratio, the nanoparticles possessed different saturated magnetization and relaxivities. SiO2 was selected for surface coating of IMO nanoparticles because dye molecules can be easily incorporated into silica shell. In addition, silica is quite biocompatible. The nanoparticles were characterized by TEM, ICP-MS, XRD and SQUID. In vivo MRI examination showed that contrast was enhanced in hippocampus, cerebellum, pituitary, submaxillary gland and kidneys of a rat in T1-weighted images, 72 h after tail vein injection.
Cell labeling is also an important field in the biomaterials application. For that purpose, we report another T2 contrast agent mFe3O4@MSN-RITC, having multiple magnetite nanoparticles attatched to a mesoporous silica nanoparticle, and simultaneously, the dye molecules conjugated into the mesoporous silica framework. The tri-functional nanoparticles possess magnetic, fluorescent property, and large surface area. In vitro examination, the cell uptake efficiency and cytotoxicity was evaluated by flow cytometry, fluorescence microscopy and WST assay. The results showed that the nanoparticles have high biocompatibility and uptake efficiency.
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dc.description.tableofcontentsTable of Contents
List of Figures Captions………………………………………………………………V
List of Scheme Captions…………………………………………………………....XIII
List of Table Captions……………………………………………………………...XIV
Chapter One Introduction…………………………………………………………...…1
1.1 Nanomaterials and Nanparticles………………………………………….1
1.1.1 Magnetic Nanoparticles……………………………………..5
(I) Co-precipitation………………………………………..7
(II) Thermal Decomposition…………………………...…10
1.1.2 Mesoporous Silica Materials………………………………14
1.2 Magnetic Resonance Imaging (MRI) and Contrast Agents…………….17
1.2.1 Principles of MRI………………………………………….17
1.2.2 Contrast of MRI………………………………………...…19
1.2.3 MRI contrast agents……………………………………….19
(I) T2 contrast agents………………………………...…..19
(II) T1 contrast agents…………………………………….26
1.3 Multifunctional Nanomaterials on Bioapplications……………...……..31
1.4 Reference……………………………………………………………….38
Chapter Two Manganese-Enhanced Magnetic Resonance Imaging of Rat Brain Based on Slow Cerebral Delivery of Mn(II) with Silica-Encapsulated MnxFe1–xO Nanoparticles……………………………………………………………………….42
2.1 Experimental Sections…………………………………………………..42
2.1.1 Materials……………………………………………………..42
2.1.2 Synthetic Procedure…………………………………………43
(1) Synthesis of Manganese Oleate Complex……….…..…43
(2) Synthesis of Manganese Iron Oxide (MIO)
Nanoparticles……………………………………………44
(3) Synthesis of Manganese Iron Oxide@silica-RITC
(MIO@SiO2-RITC) Core@shell Nanoparticles………...45
2.1.3 Characterization……………………………………………...45
(1) Transmission Electron Microscopy (TEM)…………….45
(2) Fourier Transform Infrared spectroscopy (FTIR)………46
(3) Inductively Coupled Plasma-Mass (ICP-MS)
Spectrometry…………………………………………....46
(4) X-ray Diffraction (XRD) Patterns……………………...46
(5) Magnetic Measurement………………………………...47
(6) Ultraviolet-visible (UV-visible) and Photoluminescence
(PL) Spectra………………………………………….….47
(7) Relaxivity Measurements at 0.47 T with a Minispec
Spectrometer…………………………………………….47
(8) In Vitro T1 and T2-weighted Phantom Images….……….48
(9) In Vivo MR Images with a 4.7 T System…………….…48
(10) In Vivo Biodistribution Histology…………………….…49
(11) Time-dependent Manganese and Iron Leaching
Examinations…………………………………………....50
(12) Time-dependent Manganese Ion in Blood………………50
2.2 Results and Discussion…………………………...……………………..52
2.2.1 Fourier Transform Infrared (FTIR) Spectroscopy……….....52
2.2.2 Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS)
and Energy Dispersive X-ray Spectroscopy (EDS)……….54
2.2.3 Transmission Electron Microscopy (TEM)………………...55
2.2.4 Powder X-ray Diffraction (XRD) Patterns…………………57
2.2.5 Magnetic Measurement…………………………………….58
2.2.6 MIO@SiO2-RITC Core@shell Nanoparticles……………..61
2.2.7 Photoluminescence Spectrum……………………………...65
2.2.8 Relaxivities Measurement (0.47 T) and Phantom Image (4.7
T)…………………………………………………………..65
2.2.9 In Vivo MR Images…………………………………………68
(I) MIO1@SiO2-RITC nanoparticles……………………….69
(II) MIO2@SiO2-RITC nanoparticles……………………....73
2.3 Conclusion……………………………………………………………..83
2.4 Reference………………………………………………………………85
Chapter Three Multifunctional Magnetic Mesoporous Nanoparticles and Biological Applications…………………………………………………………………………86
3.1 Experimental Section……………………………………………….…86
3.1.1 Materials…………………………………………………....86
3.1.2 Synthetic Procedure………………………………………...87
(1) Synthesis of Magnetite (Fe3O4) Nanoparticles………….87
(2) Phase Transfer of Fe3O4 Nanoparticles……………….…87
(3) Synthesis of mFe3O4@MSN-RITC and
mFe3O4@wSiO2-RITC Nanoparticles………………….88
3.1.3 Characterization…………………………………………….89
(1) Transmission Electron Microscopy (TEM), Inductively
Coupled Plasma-Mass (ICP-MS) Spectrometry, Fourier Transform Infrared spectroscopy (FTIR), and Photoluminescence (PL) Spectra………………………...89
(2) X-ray Diffraction (XRD) Patterns……………………..…89
(3) N2 Adsorption-desorption 77 K Isotherm………………...90
(4) Magnetic Measurement…………………………………..90
(5) Dynamic Light Scattering (DLS)…………………………90
(6) 60 MHz Relaxivity Measurement………………………...91
(7) In Vitro T1 and T2-weighted Phantom Images…………….91
3.1.4 In Vitro Cell Study…………………………………………...92
(1) Cell Culture……………………………………………….92
(2) Cellular Cytotoxicity Examination……………………….92
(3) Cellular Proliferation Examination……………………….94
(4) Flow Cytometry-time and Dosage Course…………….....95
(5) Confocal Microscopy…………………………………….96
(6) T2-weighted Images of Cells……………………………...97
3.2 Results and Discussion………………………………………………….99
3.2.1 Synthesis and Characterization of Magnetite (Fe3O4)
Nanoparticles………………………………………………..100
3.2.2 Phase Transfer and Mesoporous Silica Coating of Fe3O4
Nanoparticles………………………………………………..103
(I) Phase transfer………………………………………...…103
(II) Formation of Mesoporous Silica…………………....107
3.2.3 Magnetic Measurements…………………………………....111
3.2.4 Nitrogen Sorption Isotherm Measurements………………...111
3.2.5 X-ray Diffraction Patterns……………………………….…114
3.2.6 Photoluminescence Spectrum………………………………116
3.2.7 Dynamic Light Scattering (DLS) Measurements…………..116
3.2.8 Relaxivity Measurements (1.41 T) and Phantom Images (4.7
T)……………………………………………………………118
3.2.9 Investigation of Synthetic Conditions……………………...123
(I) Various quantity of CTAB in phase transfer……………124
(II) Various amount of Fe3O4@CTAB added……………...127
(III) TEOS concentration………………………………...133
3.2.10 Cell Cytotoxicity and Proliferation……………………….137
3.2.11 Confocal Microscope Image………………………………139
3.2.12 Flow Cytometry Examination………………………….…142
3.2.13 T2-weighted Cell Phantom Images………………………..149
3.3 Conclusion…………………………………………………………....151
3.4 Reference……………………………………………………………..153
Chapter Four Conclusions…………………………………………………………..154
4.1 Bi-functional (magnetism and fluorescence) MIO@SiO2-RITC nanoparticles…………………………………………………………154
4.2 Tri-functional (magnetism, fluorescence, and porosity) mFe3O4@MSN-RITC nanoparticles…………………………………155
List of Publications…………………………………………………………………156
dc.language.isoen
dc.subject磁性奈米粒子zh_TW
dc.subject細胞標的zh_TW
dc.subject中孔洞二氧化矽zh_TW
dc.subject誘導式多功能幹細胞zh_TW
dc.subject磁共振顯影劑zh_TW
dc.subjectMagnetic nanoparticlesen
dc.subjectCell labelingen
dc.subjectMesoporous silicaen
dc.subjectinduced Pluripotent Stem cellen
dc.subjectMRI contrast agentsen
dc.title多功能磁共振顯影劑在生物上之應用zh_TW
dc.titleMultifunctional Magnetic Resonance Imaging Contrast Agents for Biological Applicationen
dc.typeThesis
dc.date.schoolyear99-2
dc.description.degree碩士
dc.contributor.oralexamcommittee周必泰(Pi-Tai Chou),吳嘉文(Chia-Wen (Kevin)
dc.subject.keyword磁性奈米粒子,磁共振顯影劑,誘導式多功能幹細胞,中孔洞二氧化矽,細胞標的,zh_TW
dc.subject.keywordMagnetic nanoparticles,MRI contrast agents,induced Pluripotent Stem cell,Mesoporous silica,Cell labeling,en
dc.relation.page156
dc.rights.note有償授權
dc.date.accepted2011-08-14
dc.contributor.author-college理學院zh_TW
dc.contributor.author-dept化學研究所zh_TW
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