| 研究生: |
李儀庭 Li, Yi-Ting |
|---|---|
| 論文名稱: |
利用具有電活性之仿生脂質膜奈米粒子進行放射催化治療 Electroactive Membrane Integrated Liposome Camouflaged Nanoparticles for Radiocatalytic Treatment |
| 指導教授: |
葉晨聖
Yeh, Chen-Sheng |
| 學位類別: |
碩士 Master |
| 系所名稱: |
理學院 - 化學系 Department of Chemistry |
| 論文出版年: | 2023 |
| 畢業學年度: | 111 |
| 語文別: | 中文 |
| 論文頁數: | 148 |
| 中文關鍵詞: | 奈米粒子 、希瓦氏菌 、活性氧物質 、細胞外電子傳遞 、放射催化治療 |
| 外文關鍵詞: | Shewanella oneidensis MR-1, nanoparticle, reactive oxygen species, extracellular electron transfer, radiocatalytic treatment |
| 相關次數: | 點閱:61 下載:1 |
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癌症治療策略的研發一直是近年來炙手可熱的研究主題之一。隨著奈米科學的發展,使得半導體的金屬氧化物奈米粒子受到關注,其具有良好的光催化性能。與傳統光催化反應相比,放射催化反應能夠不受生物體組織穿透的限制,因其透過游離輻射刺激金屬氧化物奈米粒子促進化學反應的發生,產生的活性氧物質能夠毒殺癌細胞。然而,催化過程中電子電洞對重組的問題大大地降低放射催化效率。
本研究利用希瓦氏菌(Shewanella oneidensis MR-1),由於其具有細胞外電子傳遞的特性,能透過外膜上具有電子轉移能力的c型細胞色素,將電子從細胞內部傳遞至細胞外環境中的物質,形成一特殊的電子傳遞鏈。進一步地,我們透過脂質體融合細菌外膜所誘導之膜交換過程(Liposome fusion-induced membrane exchange process, LIME process),從希瓦氏菌中提取出具有電活性的脂質膜(membrane-integrated liposomes, MILs),並將其修飾於半導體奈米材料二氧化鈦(TiO2 NPs)上,形成TiO2@MIL NPs,並進行低劑量的X射線照射,評估其放射催化效率。在X射線的刺激下,TiO2@MIL NPs價帶中的電子會被激發至導帶,形成電子電洞對。由於TiO2@MIL NPs上具有電活性之MILs能夠促進電子及電洞傳遞至外部環境中與氧氣及水反應,產生大量的超氧化物及羥基自由基,達到增強放射催化的功效。在體外細胞實驗中,也證實在1 Gy的X射線照射下,TiO2@MIL NPs於肝癌細胞中產生之大量超氧化物及羥基自由基能進一步導致癌細胞毒殺作用並觀察到其DNA受損的情形。最後,經由原位肝腫瘤之小鼠模型作為評估體內抗腫瘤效率的動物實驗證實,在1 Gy的X射線照射下,TiO2@MIL NPs能夠抑制小鼠體內生物發光訊號,表明肝腫瘤的生長受到抑制,具有優秀的放射催化治療的功效。
Metal oxide nanoparticles are semiconductors that have the ability to undergo radiocatalytic reactions, making them suitable for application in radiocatalytic cancer treatment. However, these materials often face challenges in minimizing the recombination of electron-hole pairs during radiocatalysis. Recent studies have highlighted the unique capabilities of Shewanella (S.) oneidensis MR-1, a bacterium known for its ability to perform extracellular electron transfer (EET). In this study, we utilized the liposome fusion-induced membrane exchange process to obtain electroactive membrane integrated liposomes (MILs) from S. oneidensis MR-1. Subsequently, we coated the MILs onto the surface of TiO2 NPs to form TiO2@MIL NPs. The presence of c-type cytochromes on MILs enables efficient electron transfer capabilities. After a low dose (1 Gy) of X-ray irradiation, TiO2@MIL NPs demonstrated a higher production of superoxide and a small quantity of hydroxyl radicals compared to the other control groups. The above observation confirms the enhancement of radiocatalytic efficiency in TiO2@MIL NPs. Moreover, this phenomenon was consistently observed in both in vitro and in vivo experimental settings, leading to serious cytotoxicity toward hepatoma cells and inhibition of tumor growth. Taken together, these findings provide compelling evidence for the remarkable capacity for TiO2@MIL NPs to effectively combat cancer through their exceptional radiocatalytic efficiency.
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