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標題: | 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 Preparation and evaluation of Ce-doped TiO2 conjugated with PHA-E activated by physical stimulus for lung cancer treatment |
作者: | Chun-Chen Yang 楊鈞程 |
指導教授: | 段維新(Wei-Hsing Tuan) |
共同指導教授: | 林?輝(Feng-Huei Lin) |
關鍵字: | 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, X-ray,ultrasound,TiO2:Ce@SiO2-PEG-(PHA-E),reactive oxygen species,alternative cancer therapy, |
出版年 : | 2019 |
學位: | 博士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72640 |
DOI: | 10.6342/NTU201902151 |
全文授權: | 有償授權 |
顯示於系所單位: | 材料科學與工程學系 |
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