臺灣博碩士論文加值系統

光驅動的治療方式是近年來興起的一種癌症治療方法。相較於外科手術的程度，光熱治療有著較低侵入是以及低副作用的優點。在許多的光熱試劑當中能存在生物相容性的一大問題尤其在銅的材料當中。雖然我們開發出一個具有進紅外光吸收的核殼結構氧化銅奈米粒子，但當氧化銅奈米粒子材料進入到細胞培養液發現此材料對於胺基酸的親和性較高使得崩解及破壞結構的速率較高，因此在氧化銅材料對於在細胞培養液裡的穩定性是一大的課題。
為了解決氧化銅在細胞培養液的穩定性，本篇研究嘗試了不同方式保護奈米粒子對於穩定性之改善並不顯著，另外我們使用加入另一金屬前驅物來合成而形成了一個銅-金雙金屬的複合體來增加其穩定性。在光熱的表現上有較佳的表現，且在材料照光後的穩定性上在我們的測試中也有相當的光穩定性，在光熱轉換效率的表現上也有。在細胞的測試中，在尚未照射雷射情況下，材料並未看出明顯的毒性; 當提供雷射808 nm的輔助下，可以發現細胞存活率抑制到約20%。因此，銅-金雙金屬的複合體不僅降低了銅離子的釋放也增加了在細胞培養液的穩定性，在光熱治療上也有相當的助益，相信日後可以成為一個具有潛力的光熱試劑應用在癌症治療上。

Photothermal therapy (PTT) was an innovate therapy that received many attentions due to its low invasive property. However, the vast phototheraml agents had biocompatibility problem especially copper based series agents. We focused on improvement the Cu@Cu2O stability in culture medium due to its high affinity and dissolution rate too fast that led to limitation in vitro application. Therefore, we attempted to different approaches to protect the Cu@Cu2O or Cu@Cu2O@HA modification on that NPs surface. However, these approach was modified to the Cu@Cu2O or Cu@Cu2O, the stability no obviously was improved. Eventually, we directly added another metal to reform the bimetallic nanocomposites (NCs). In addition, The Cu-Au bimetallic NCs exhibited excellent photothermal performance that remain original similar photothermal property due to their strong near-infrared (NIR) absorption property. The size of Cu-Au bimetallic NCs detected by TEM about 10 nm and this size could through passive targeting due to enhance permeability and retention (EPR) effect. Moreover, improvement stability in culture medium of the Cu-Au bimetallic NCs. In vitro experiment indicated Cu-Au bimetallic NCs without 808 nm laser irradiation reveal low cytotoxicity, whereas, the almost 20% cells survival with laser irradiation in cancer cells. Consequently, the bimetallic NCs not only possessed excellent photothemral efficiency but increase biocompatibility via reducing the copper ions release in biomedical application.

致謝辭 i
Table of Contents ii
中文摘要 iv
Abstract v
List of Figures vi
List of Table x
Chapter 1 Introduction 1
1.1 Cancer 1
1.2 Photothermal Therapy 2
1.3 Copper Series Inorganic Material 7
1.4 The Risk of Copper 8
Chapter 2 Experimental Design and Methods 12
2.1 Experimental Design 12
2.2 Material 13
2.3 Characterization 15
2.4 Preparation of Cu@Cu2O Nanoparticles 15
2.5 Modification of Cu@Cu2O Nanoparticles 16
2.5.1 Preparation of Cu@Cu2O@HA Nanoparticles 16
2.5.2 Preparation of Cu@Cu2O@HA to growth CaP 16
2.5.3 Preparation of Cu@Cu2O to growth CaP 16
2.5.4 Preparation of Cu@Cu2O@HA to attach chitosan 17
2.5.5 Preparation of Cu-Au Bimetallic Nanocomposites 17
2.6 Photothermal Effect Evaluation 17
2.7 Copper Ions Release Profile 18
2.8 Cell line and Cell Culture Conditions 18
2.9 Cell Culture and Cytotoxicity Studies 18
2.10 Photothermal Ablation of Cancer Cells In Vitro 19
2.10.1 Observed by Cytotoxicity 19
2.10.2 Observed by Confocal Microscopy Image 20
Chapter 3 Results and Discussion 21
3.1 Synthesis and Characterizations of Copper Series Nanoparticles 21
3.2 Evaluation of Photothermal Ability 40
3.3 Stability of Copper Series Nanoparticles 46
3.4 In Vitro Photothermal Effect and Cell Viability Study 50
3.5 In Vitro Investigation by Optical Microscopy and Flow 53
Chapter 4 Conclusion 59
Reference 60

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