氣體響應性分子藥物應用於癌症化學治療｜國立臺灣科技大學博碩士論文系統

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研究生：	武垂天銀 VO THUY THIEN NGAN
論文名稱：	氣體響應性分子藥物應用於癌症化學治療 GAS-RESPONSIVE MOLECULAR DRUG FOR CANCER CHEMOTHERAPY
指導教授：	鄭智嘉 Chih-Chia Cheng
口試委員:	謝永堂 Yeong-Tarng Shieh 楊長謀 Chang-Mou Yang 戴子安 Chi-An Dai 陳建光 Jem-Kun Chen 莊偉綜 Wei-Tsung Chuang 鄭智嘉 Chih-Chia Cheng
學位類別：	碩士 Master
系所名稱：	應用科技學院 - 應用科技研究所 Graduate Institute of Applied Science and Technology
論文出版年：	2022
畢業學年度：	110
語文別：	英文
論文頁數：	118
中文關鍵詞：	氣體響應性分子、癌症
外文關鍵詞：	gas-responsive, hypercapnia
相關次數：	點閱：166 下載：0
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上一筆

最常見的癌症治療方法是化學療法，儘管它仍然存在一些非特異性的缺點。在本論文中，我們成功地從有機染料羅丹明 6G 和含胺部分 (RI) 中開發出一種新型分子藥物，該藥物極有可能用作靶向癌症治療的化學劑。該衍生物具有CO2反應能力，可改變溶解度等物理特性，並包裹在載體中進行靶向治療。我們通過單晶 X 射線衍射、核磁共振光譜、質譜和元素分析來定義成功的合成。之後，仔細分析了 CO2 響應特性，以明確溶解度轉換以及質子化引起的其他物理特性轉換。為了應用於化療，RI 被一種含氫鍵的載體 (UrCyPEG) 封裝，該載體對低 pH 值的腫瘤內環境作出反應以釋放藥物。所獲得的負載 RI 的納米顆粒在血清中表現出長期的結構穩定性，並通過共同觸發 pH/CO2 顯著增加藥物釋放。更值得注意的是，一系列體外生物測試表明負載 RI 的納米顆粒對癌細胞具有高選擇性細胞毒性，而對正常細胞無害，這意味著 CO2 響應特性和氫鍵在增強誘導細胞凋亡和選擇性細胞毒性方面的重要作用由於共同作用的 pH/CO2 腫瘤內環境。

The most common approach for cancer treatment is chemotherapy, although it remains several shortcomings as non-specific. In this thesis, we successful developed a novel molecular drug from an organic dye Rhodamine 6G and amine-containing moiety (RI) that is highly possible to utilize as a chemo-agent for targeted cancer treatment. This derivative possesses ability of CO2-response to switch physical characteristic such as solubility and wrapped in a carrier for targeted treatment. We define the successful synthesis by Single-crystal X-ray Diffraction, Nuclear Magnetic Resonance Spectroscopy, Mass spectra and Elemental analysis. Afterward, the CO2-responsive properties were careful analysed to make clear of the solubility switching as well as the other physical characteristic transformation by protonation. To be applied in chemotherapy, RI was encapsulated by a hydrogen-bonding containing carrier (UrCyPEG) that responses to low pH intratumor environment for drug release. The achieved RI-loaded nanoparticles exhibit a long-term structural stability in serum and significant increase in drug release by co-trigger pH/CO2. More attentionally, a sequence of in vitro biological tests illustrates the high selective cytotoxicity of RI-loaded nanoparticles towards cancer cells whereas remains unharmful in normal cells, implying the vital role of CO2-responsive properties and hydrogen bonding in enhance of inducing apoptosis and selective cytotoxicity due to co-effect pH/ CO2 intratumor environment.

ABSTRACT    II
ACKNOWLEADGEMENT    IV
I.INTRODUCTION    1
I.1. Background of study    1
I.2. Objective of the thesis    4
II. LITURATURE REVIEW    5
II.1. Overview of Cancer    5
II.2. Therapeutic of Cancer Modalities    12
II.2.1 Surgery    12
II.2.2. Radiation Therapy    13
II.2.4. Hyperthermia Therapy    16
II.2.5. Gene therapy    17
II.2.5.1. Immunotherapy    17
II.2.5.2. Oncolytic viro remedy    20
II.2.5.3. Gene transfer    20
II.2.6. Stem Cells in Cancer Treatment    21
II.3. Nanomedicine in Cancer Therapy    24
II.3.1. Principle of Nanomedicine    24
II.3.2. Advanced Functionalities Nanomedicine in Cancer Therapy    26
II.4. Nanocarrier for Cancer Therapy    31
II.4.1. Linear polymers    31
II.4.2. Dendrimer, the multivalent polymeric systems    32
II.4.3. Liposomes and micelles    32
II.4.4. Non-polymeric nanoparticles    33
II.4.5. Niosomes    34
II.4.6. Solid lipid nanoparticles (SLNs)    35
II.4.7. Nanobubles    35
II.5. CO2-reponsive material    36
II.6. Rhodamine 6G    37
II.7. Imidazole-containing molecules    38
II.8. Ureido Cytosine PEG    39
III. EXPERIMENTAL DESIGN    40
3.1. Materials    40
3.2 Cell experiment materials    41
3.3 Experimental equipment and parameters    43
3.3.1 (Rotary Evaporator)    43
3.3.2 Fourier transform infrared spectroscopy    43
3.3.3 UV/Vis Spectrophotometer    44
3.3.4 Photoluminescence Spectroscopy    44
3.3.5. CO2 incubator    44
3.3.6. Centrifuge    45
3.3.7.  Vortex Mixer    45
3.3.8. ELISA Reader    45
3.3.9. Fluorescence Microscope    45
3.3.10. Flow Cytometry    46
3.3.11. Nuclear Magnetic Resonance spectroscopy    46
3.3.12. Dynamic Light Scattering    47
3.3.13. Atomic force microscope    47
3.3.14. Spin Coater    48
3.3.15. Scanning Electron Microscope    48
3.3.16. Elemental Analyzer    49
3.3.17. Mass Spectrometry    49
3.3.18. pH meter    49
3.4. Synthesis RI and UrCyPEG    50
3.5 Sample preparation    51
3.5.1 Polymer preparation    51
3.5.2. Preparation of drug micelles    51
3.5.3. Drug Concentration Calibration Line    52
3.5.4 Drug loading capacity    52
3.5.5. In vitro drug release simulation    52
3.5.6 Nanoparticle stability test    53
3.5.7 Nanoparticle stimulation response test    53
3.5.8. Gas responsive test    53
3.5.6. Hemolysis assay    54
3.6 Cell biological preparation    55
3.6.1 Hela cell culture medium    55
3.6.2 3T3 cell culture medium    55
3.6.3 Cell thawing culture    55
3.6.4 Cell Subculture    55
3.6.6 Cell Biological Toxicity Test    56
3.6.7 Preparation of Fluorescence Microscope    56
3.6.8 Preparation of Annexin-binding buffer    57
IV. RESULTS AND DISCUSSION    58
4.1. Synthesis RI    58
REFERENCES    99

                                

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全文公開日期 2027/01/24 (校內網路)
全文公開日期 2027/01/24 (校外網路)
全文公開日期 2027/01/24 (國家圖書館：臺灣博碩士論文系統)

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