臺灣博碩士論文加值系統

此研究中，我們以光感藥物為起始劑聚合成光感性高分子，且本材料亦可進一步塞入順磁性金屬離子。我們利用NMR、GPC，吸收和螢光光譜來對此兩種光感性的高分子材料進行性質分析測定。而此疏水的光感性高分子利用溶劑揮發法於水溶液可自行組裝製備成奈米粒子，在活性氧化物質(ROS)測定的結果顯示出，於水溶液中奈米粒子比起單純的光感藥物能更有效的產生ROS，這是由於水溶液中奈米粒子具有良好的分散型態。此結果顯示出本實驗中的奈米粒子作為光動力治療於醫學材料上的潛力。另一項結果顯示塞入順磁性金屬離子的奈米粒子具有核磁共振顯影的效果，能夠發展作為核磁共振顯影劑於癌症診斷上的潛力。未來，我們能夠結合此兩種光感性的高分子材料應用在癌症的診斷治療上。

In this study, photosensitizer core polymers without or with paramagnetic metal ion insertion were synthesized and characterized. The synthesized photosensitizer-centered polymer assembled into stable nanoparticles that improved the solubility of the photosensitizer and prevented their aggregation. Our results show that higher levels of reactive oxygen species (ROS) were generated from the nanoparticles than from the free photosensitizer due to aggregation of the hydrophobic photosensitizer. The results indicate that nanoparticles should be considered as a potential biomaterial for use in a photodynamic therapy (PDT) for cancer treatment. Our results also show that the particles with insertion of paramagnetic metal can be a contrast agent for magnetic resonance imaging (MRI) application. Thus, these nanoparticles are potentially good candidates as theranostic agents in the future.

Acknowledgement............................................i
中文摘要..................................................ii
Abstract.................................................iii
List of Figures..........................................vii
List of Tables............................................xi
Chapter 1: Introduction....................................1
1-1 Magnetic Resonance Imaging.............................1
1-1-1 Mechanisms of MR Contrast............................1
1-1-2 MR Contrast Image....................................2
1-1-3 Spin-Lattice Relaxation (Longitudinal Relaxation)....4
1-1-4 Spin-Spin Relaxation (Transverse Relaxation).........5
1-1-5 Contrast Agents......................................7
1-2 Biologically Activated MR contrast agents..............9
1-3 Photodynamic Therapy for Cancer.......................10
1-4 Nanoparticles with PDT or MRI functions...............12
Chapter2: Experimental Design and Method..................14
2-1 Experimental Design...................................14
2-2 Instruments...........................................14
2-3 Materials.............................................15
2-4 Experimental Methods..................................16
2-4-1 Synthesis of Chlorin e6-Poly(ε-caprolactone) Conjugate.................................................16
2-4-2 Insertion of Manganese Ion into Chlorin e6 Poly(ε-caprolactone) Polymers....................................17
2-4-3 Preparation of CPCL or Mn-CPCL Nanoparticles........18
2-4-4 Detection of ROS Produced by CPCL Polymer/Nanoparticles.....................................18
2-4-5 In Vitro MR Images..................................19
2-4-6 Cell Line and Culture Conditions....................19
2-4-7 Cytotoxicity and Phototoxicity of CPCL or Mn-CPCL Nanoparticles in MCF-7/ADR Cells..........................20
Chapter 3: Results and Discussion.........................22
3-1 Characterization of CPCL Polymers.....................22
3-1-1 Synthesis and Characterization of CPCL Polymers.....22
3-1-2 UV-Vis and Fluorescence Spectra of CPCL Polymers....24
3-2 Characterization of Mn-CPCL Polymers..................26
3-2-1 Structure of Manganese Ions Inserted into CPCL Polymers..................................................26
3-2-2 UV-Vis and Fluorescence Spectra of Mn-CPCL Polymers.29
3-2-3 Amount of Manganese in Mn-CPCL Polymers.............30
3-3 Characterization of CPCL Nanoparticles................31
3-3-1 Size Distribution of CPCL Nanoparticles.............31
3-3-2 Morphology of CPCL Nanoparticles....................32
3-3-3 Stability of CPCL Nanoparticles.....................33
3-3-4 UV-Vis and Fluorescence Spectra of CPCL Nanoparticles.............................................34
3-3-5 ROS generation of CPCL Polymer/Nanoparticles........38
3-4 Characterization of Mn-CPCL Nanoparticles.............40
3-4-1 Size distribution of Mn-CPCL Nanoparticles..........40
3-4-2 Morphology of Mn-CPCL Nanoparticles.................40
3-4-3 Stability of Mn-CPCL Nanoparticles..................42
3-4-4 UV-Vis and Fluorescence Spectra of Mn-CPCL Nanoparticles.............................................43
3-4-5 Amount of Manganese Determine of CPCL Nanoparticles.45
3-5 In Vitro MR Images....................................45
3-6 Cytotoxicity and Phototoxicity of CPCL and Mn-CPCL Nanoparticles in MCF-7/ADR Cells..........................48
Chapter 4: Conclusions....................................50
Reference.................................................51

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