以X光為光源照射摻雜碳的二氧化鈦多孔奈米粒子產生自由基用於腫瘤治療

Porous C-doped TiO2 nanoparticles exposed to X-ray to induce free radicals for tumor treatment

蔡敏雄(Min-Hsiung Tsai)

指導教授 ： 林峯輝

國立臺灣大學/工學院/醫學工程學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201601799

摘要

光動力療法係利用光敏感藥物被特定波長的光激發來治療癌症，因只有照光區域才會受到影響，故相較於其他療法，副作用較輕。然而受限於光敏感藥物及光源的選擇，穿透深度不足，只能治療較表層的癌症，且若腫瘤體積太大時，治療效果亦不佳。本研究試圖改善此一缺點而提出一套方法：以穿透深度較深的X光來激發自行合成的材料—摻雜碳的二氧化鈦奈米粒子(TiO2:C)，使其產生自由基，殺死腫瘤細胞。
本研究以溶膠凝膠法成功合成出摻雜碳的二氧化鈦(TiO2:C)，表面粗糙且具有孔洞結構，奈米顆粒大小約在200 - 300 nm之間，並具有O-Ti-C三者的鍵結，使得能隙大小降為3.07eV，較一般未摻雜的TiO2還要低。此外TiO2:C經過X光激發後會產生自由基，成功降解亞甲基藍溶液。
在細胞實驗的部分，不論是用WST-1或LDH試驗，皆證明本材料具生物相容性；將TiO2:C以X光激發，發現對於A549癌細胞之毒殺效果良好，第三天可達30%。動物實驗的部分，本材料相當安全，注射材料後，裸鼠生理狀況正常、血液生化分析及組織病理切片沒有異狀；在成功接種A549在裸鼠皮下形成腫瘤後，注射TiO2:C材料液並以X光激發，能有效抑制腫瘤的生長甚至縮小其體積。
綜合上述，將TiO2:C以X光來激發，會產生自由基，使其無論是在有機物的降解、細胞實驗和動物實驗中，皆有極好的效果，應為一套可行的方法。未來除了調整參數讓效果更好之外，也能往人體臨床的方向進行，相信可以造福更多癌症的病友。

關鍵字

腫瘤治療 ； 光動力療法 ； 碳摻雜二氧化鈦 ； X光 ； 自由基 ； 活性氧物質

並列摘要

Among many cancer therapies, photodynamic therapy is the one which causes less side effects due to the small area illuminated by the light with specific wavelength to excite the photosensitizer. However, the therapy is limited by its penetration depth because of the selection of photosensitizer and light source. Only tumors on the surface of the body could be treated, for example, skin cancer, and head and neck cancer. The study tried to solve this problem by providing a method that tumor cells could be killed by free radicals which were produced by the synthesized material (TiO2:C) excited by X-ray. X-ray could penetrate deeper than other light source but was not so much harmful as gamma ray.
TiO2:C with rough surface and porous structures was synthesized successfully by the sol-gel method. The size of the particles was between 200 - 300 nm. The observed formation of the bonding of O-Ti-C could narrow its band-gap to 3.07 eV which is lower than undoped TiO2. In addition, under X-ray exposure, TiO2:C produced free radicals so that Methylene blue was degraded.
TiO2:C was proved biocompatible through WST-1 and LDH assay for 3T3 cell. In terms of in vitro study, after immersed in the medium with TiO2:C powder and excited by X-ray, the cytotoxicity of tumor cell, A549, was larger than control group for continuous 2 days. As for in vivo study, the safety of synthesized TiO2:C was proved when examining the physical condition, the blood biochemical analysis, and histological analysis of BALB/c nude mice. Tumors appeared successfully after subcutaneous injection of A549 tumor cells to nude mice. When treated with TiO2:C injection followed by X-ray exposure, growing of tumors was inhibited.
In summary, the method was of great effect for degradation of organic dye, in vitro study, and in vivo study. In the future, better experimental parameters might be needed, and clinical trials for human might be conducted. Then, a new way for photodynamic therapy and a better life for those suffered cancer could be expected

並列關鍵字

Tumor treatment ； Photodynamic therapy ； TiO2:C ； X-ray ； free radicals ； ROS

參考文獻

[8] Society AC. How chemotherapy drugs work. Chemotherapy 2016.

[10] Society AC. What is targeted cancer therapy? Targeted Cancer Therapy 2016.

[12] 趙榮杰、張隆基. T細胞輸入療法-癌症治療新境界. 臺灣醫界 2010; 53: 452~4

[2] 衛生福利部中央健康保險署. 103年全民健康保險統計. 資訊公開 2015.

[3] 衛生福利部中央健康保險署. 103年各類癌症健保前10大醫療支出統計. 104年衛生福利部新聞 2015.