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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 段維新(Wei-Hsing Tuan) | |
| dc.contributor.author | Chun-Chen Yang | en |
| dc.contributor.author | 楊鈞程 | zh_TW |
| dc.date.accessioned | 2021-06-17T07:02:30Z | - |
| dc.date.available | 2019-08-19 | |
| dc.date.copyright | 2019-08-19 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-07-30 | |
| dc.identifier.citation | 1. Torre, L.A., R.L. Siegel, and A. Jemal, Lung Cancer Statistics. Adv Exp Med Biol, 2016. 893: p. 1-19.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72640 | - |
| dc.description.abstract | 傳統光動力療法因為光敏劑及照射光源的選擇，而有著穿透深度的侷限。本研究採用改良的溶膠凝膠法合成摻雜鈰的二氧化鈦作為被低劑量X光激發的光敏劑，危害較游離輻射小，且可產生細胞內活性氧分子ROS。人類肺腺癌A549細胞株用於體外和體內模型以評估X光照射摻雜鈰的二氧化鈦誘導細胞死亡的功效，在低劑量X光照射摻雜鈰的二氧化鈦下，細胞活性顯著降低。乳酸脫氫脢LDH 分析顯示，在X光照射摻雜鈰的二氧化鈦對A549細胞具有細胞毒性。相較於未照射X光的材料，X光照射摻雜鈰的二氧化鈦會產生顯著的細胞內活性氧分子，促進A549細胞凋亡/壞死。同時，摻雜鈰的二氧化鈦可以增強X光誘導光動力療法的功效，並且使體內腫瘤生長受到抑制。由X光激發摻雜鈰的二氧化鈦誘導細胞毒性，從而抑制腫瘤生長的ROS生成機制也會在本篇研究中探討。
聲動力療法也是一種有效的治療方法，透過超音波照射激發聲敏劑在病患體內產生自由基來殺死腫瘤細胞。我們使用植物凝集素E之鈰摻雜二氧化鈦作為聲敏劑，透過空化效應，產生過量的ROS殺死癌細胞。使用霧化器以吸入方式給予顆粒之體內模式也被確認。透過肺部的蘇木素-伊紅染色也證實了腫瘤的抑制。在實驗組和未治療組之間主要器官並無觀察到副作用跡象以及肺水腫。 植物凝集素E之鈰摻雜二氧化鈦可作為潛在的聲敏劑用於肺癌治療。 | zh_TW |
| dc.description.abstract | Photodynamic therapy (PDT) is limited by its penetration depth because of the selection of photosensitizer and light source. In this study, Ce-doped TiO2 (TiO2:Ce) was synthesized by a modified sol-gel method to act as a photosensitizer activated by low-dose X-rays, less harmful than ionizing radiation, to generate intracellular reactive oxygen species (ROS). The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-irradiated TiO2:Ce to induce cell death. The cell viability significantly decreased with TiO2:Ce exposure under low-dose X-ray irradiation. An LDH assay showed that intracellular TiO2:Ce under X-ray irradiation was cytotoxic to A549 cancer cells. TiO2:Ce produced significant ROS under low-dose X-ray irradiation and promoted apoptosis/necrosis of A549 cancer cells. TiO2:Ce can enhance the efficacy of X-ray-induced PDT, and tumor growth was inhibited in vivo. The mechanisms underlying ROS generation by TiO2:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed.
Sonodynamic therapy is an effective treatment for eliminating tumor cells by irradiating sonosentitizer in patient’s body with higher penetration ultrasound and inducing the free radicals. We used TiO2:Ce@SiO2-PEG-(PHA-E) as the sonosensitizer which could be activated by ultrasound to cause cavitation effect to generate excess amount of ROS to kill cancer cells. The effect of aerosol delivery was confirmed in vivo. The inhibition of tumor was also confirmed by H&E staining of lungs. Undetectable physiological morphology changes were observed between the experimental group and non-treated group, including no observable signs of side effects on major organs from H&E staining, and there should be no lung edema after TiO2:Ce@SiO2-PEG-(PHA-E) inhalation. TiO2:Ce@SiO2-PEG-(PHA-E) could be a potential sonosensitizer under ultrasound irradiation for lung cancer treatment. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T07:02:30Z (GMT). No. of bitstreams: 1 ntu-108-D03527007-1.pdf: 7561563 bytes, checksum: b8a24838ef05fced8877b3dae8b240e8 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝 I
摘要 II ABSTRACT IV List of Figures IX List of Tables XI Chapter 1 Introduction 1 1.1 Lung cancer 1 1.1.1 Clinical classification 2 1.1.2 Lung cancer staging 3 1.1.3 Lung cancer treatment 6 1.2 Photodynamic therapy (PDT) 11 1.3 Sonodynamic therapy (SDT) 11 1.4 Epidermal growth factor receptor 11 1.5 Purpose of the study 12 Chapter 2 Theoretical basis 14 2.1 Photodynamic therapy (PDT) 14 2.1.1 Mechanisms 14 2.1.2 Light source 16 2.1.3 Photosensitizer 19 2.2 Sonodynamic therapy (SDT) 24 2.2.1 Mechanisms 24 2.2.2 Ultrasound 26 2.2.3 Sonosensitizer 26 2.3 Titanium dioxide (TiO2) 28 2.4 Doping mechanism of TiO2 30 2.5 Phytohemagglutinin erythroagglutinating 30 Chapter 3 Materials and methods 32 3.1 Materials 32 3.1.1 Chemicals and reagents 32 3.1.2 Instruments 33 3.2 Flow chart 33 3.3 Preparation of TiO2 and TiO2:Ce for in vitro and in vivo study 35 3.3.1 Preparation of TiO2 and TiO2:Ce 35 3.3.2 Characterization of TiO2 and TiO2:Ce 37 3.3.3 In vitro study 38 3.3.4 In vivo study 42 3.3.5 Statistical analysis 44 3.4 Preparation of TiO2:Ce@SiO2-PEG-(PHA-E) for in vitro and in vivo study 44 3.4.1 Preparation of TiO2:Ce@SiO2-PEG-(PHA-E) 44 3.4.2 Characterization of TiO2:Ce@SiO2-PEG-(PHA-E) 47 3.4.3 Detection of hydroxyl radicals 47 3.4.4 In vitro study 47 3.4.5 In vivo study 51 Chapter 4 Results 56 4.1 PDT effect of synthesized TiO2:Ce under X-ray irradiation 56 4.1.1 Material characterization 56 4.1.2 Cell viability and cytotoxicity 59 4.1.3 ROS generation of developed TiO2 and TiO2:Ce under X-ray irradiation 61 4.1.4 Effect of TiO2 and TiO2:Ce in PDT in vitro 62 4.1.5 Effect of synthesized TiO2:Ce under X-ray irradiation on apoptosis/necrosis 64 4.1.6 Effect of the synthesized TiO2:Ce on tumor growth under X-ray irradiation in vivo 66 4.1.7 Blood/serum analysis and H&E examination 67 4.2 SDT effect of synthesized TiO2:Ce@SiO2-PEG-(PHA-E) under ultrasound irradiation 69 4.2.1 Material characterization 69 4.2.2 Hydroxyl radicals generation of TiO2:Ce@SiO2-PEG-(PHA-E) under ultrasound irradiation 74 4.2.3 ROS generation of TiO2:Ce@SiO2-PEG-(PHA-E) under ultrasound irradiation 75 4.2.4 Effect of TiO2:Ce@SiO2-PEG-(PHA-E) in SDT in vitro 77 4.2.5 Effect of TiO2:Ce@SiO2-PEG-(PHA-E) in SDT on Live/dead assay 78 4.2.6 Effect of TiO2:Ce@SiO2-PEG-(PHA-E) in SDT on tumor growth under ultrasound irradiation in vivo 80 4.2.7 In vivo safety testing by blood/serum analysis and H&E examination of TiO2:Ce@SiO2-PEG-(PHA-E) in SDT 82 4.2.8 Biodistribution of TiO2:Ce@SiO2-PEG-(PHA-E) in SDT in vivo 89 4.2.9 Acute lung injury assay of TiO2:Ce@SiO2-PEG-(PHA-E) in SDT 89 Chapter 5 Discussion 91 5.1 Characterization of TiO2:Ce 91 5.2 In vitro ROS generation and cytotoxicity of TiO2:Ce under X-ray irradiation 93 5.3 In vivo antitumor efficacy of TiO2:Ce under X-ray irradiation 96 5.4 Characterization of TiO2:Ce@SiO2-PEG-(PHA-E) 96 5.5 ROS evaluation of TiO2:Ce@SiO2-PEG-(PHA-E) under ultrasound irradiation 97 5.6 In vitro ROS generation and cytotoxicity of TiO2:Ce@SiO2-PEG-(PHA-E) under ultrasound irradiation 99 5.7 In vivo antitumor efficacy of TiO2:Ce@SiO2-PEG-(PHA-E) under ultrasound irradiation 101 Chapter 6 Conclusion 103 Reference 105 | |
| dc.language.iso | en | |
| dc.subject | 植物凝集素E之鈰摻雜二氧化鈦 | zh_TW |
| dc.subject | 替代性癌症療法 | zh_TW |
| dc.subject | 細胞內活性氧分子 | zh_TW |
| dc.subject | X光 | zh_TW |
| dc.subject | 超音波 | zh_TW |
| dc.subject | X-ray | en |
| dc.subject | reactive oxygen species | en |
| dc.subject | alternative cancer therapy | en |
| dc.subject | TiO2:Ce@SiO2-PEG-(PHA-E) | en |
| dc.subject | ultrasound | en |
| dc.title | 製備與評估以物理刺激結合植物凝集素E之鈰摻雜
二氧化鈦於肺癌治療之運用 | zh_TW |
| dc.title | Preparation and evaluation of Ce-doped TiO2 conjugated with PHA-E activated by physical stimulus for lung cancer treatment | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 林?輝(Feng-Huei Lin) | |
| dc.contributor.oralexamcommittee | 黃義侑(Yi-You Huang),郭士民(Shyh-Ming Kuo),陳博洲(Po-Chou Chen) | |
| dc.subject.keyword | X光,超音波,植物凝集素E之鈰摻雜二氧化鈦,細胞內活性氧分子,替代性癌症療法, | zh_TW |
| dc.subject.keyword | X-ray,ultrasound,TiO2:Ce@SiO2-PEG-(PHA-E),reactive oxygen species,alternative cancer therapy, | en |
| dc.relation.page | 113 | |
| dc.identifier.doi | 10.6342/NTU201902151 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-07-31 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 材料科學與工程學研究所 | zh_TW |
| 顯示於系所單位： | 材料科學與工程學系 | |
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