| 研究生: |
黃責強 Huang, Ze-Jiung |
|---|---|
| 論文名稱: |
鈀活化二維氧化鎳之光動力治療與化學動力治療膀胱癌 Palladium-elicited Two-Dimensional Nickel Oxide for Photodynamic and Chemodynamic Therapy of Bladder Cancer |
| 指導教授: |
黃志嘉
Huang, Chih-Chia |
| 學位類別: |
碩士 Master |
| 系所名稱: |
理學院 - 光電科學與工程學系 Department of Photonics |
| 論文出版年: | 2024 |
| 畢業學年度: | 112 |
| 語文別: | 英文 |
| 論文頁數: | 99 |
| 中文關鍵詞: | 氧化鎳 、奈米酶 、鈀 、催化 、光熱 、化學動力 、癌症治療 |
| 外文關鍵詞: | Nickel oxide, Nanozyme, Palladium, Catalyze, Photothermal, Chemo dynamic, Cancer therapy |
| 相關次數: | 點閱:28 下載:0 |
| 分享至: |
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近年來,奈米酵素酶的高度催化活性在抗癌治療中引起了廣泛的關注。然而,大多數的奈米酵素酶僅具有一種或兩種酵素功能,且容易被細胞中的抗氧化防禦機制所抑制,導致治療成效不佳。
在此,我們設計了一種新型的二維鈀摻雜氧化鎳奈米酵素酶,利用雙金屬摻雜系統,賦予本身高度穩定但沒有催化活性的氧化鎳分子多種催化活性,並使其能夠以多種方式調節細胞內的氧化壓力。當癌細胞內過度表達的H¬2O2與NiO:Pd奈米酵素酶反應時,氫氧自由基 (·OH) 和單態氧 (1O2) 的生成明顯增強。同時,也觀察到了NiO:Pd奈米酵素酶模擬類過氧化氫酶 (CAT) 所產生的氧氣。其中我們也闡明了各種催化反應的基本機制與原理。此外,在波長635 nm的雷射照射下,NiO:Pd奈米酵素酶表現出光熱特性。溫度的升高可以增強其與H2O2反應的生物催化活性,導致膀胱癌細胞的存活率下降到40%以下。最後,由於NiO:Pd奈米酵素酶的產氧特性,我們也結合了具有生物安全性的鐵葉綠素光敏劑。利用奈米酵素酶自發性的產氧特性,除了能夠逆轉腫瘤微環境中的缺氧狀況,還進一步提升光動力治療的效果。
這項工作代表了一種合成氧化鎳奈米酶的新方法,透過利用貴金屬摻雜和光熱能力來增強活性氧分子的產生,實現聯合治療,並逆轉腫瘤微環境中的免疫抑制。
In recent years, the high catalytic activity of nanozymes has garnered significant attention in cancer therapy. However, most nanozymes possess only one or two enzymatic functions and are easily inhibited by the cell's antioxidant defense mechanisms, resulting in suboptimal therapeutic efficacy. Herein, we have designed a novel 2D nanozyme composed of palladium-doped nickel oxide. By doping with a bimetallic system, the inherently stable but catalytically inactive nickel oxide is endowed with multiple catalytic activities, allowing it to modulate intracellular oxidative stress in various ways. The generation of hydroxyl radicals and additional singlet oxygen (1O2) species was enhanced when H2O2 reacted with the NiO:Pd nanozymes. Concurrently, oxygen production from the catalase-like (CAT) activity of the nanozyme was observed. We also elucidated the underlying mechanisms of the various catalytic reactions. Additionally, under 635 nm laser irradiation, NiO:Pd nanozymes exhibited photothermal properties. The temperature increase could enhance its biocatalytic activity upon reaction with H2O2, leading to efficient killing of bladder cancer cells with a viability reduction of below 40%. Moreover, due to the oxygen-generating properties of the NiO:Pd nano-enzyme, we also incorporated a biocompatible iron chlorophyll photosensitizer. Utilizing the spontaneous oxygen production of the nanozymes, we were able to reverse the hypoxic conditions within the tumor microenvironment and further enhance the efficacy of photodynamic therapy. This work represents a novel approach in synthesizing NiO nanozymes by employing noble metal doping and photothermal capabilities to enhance ROS generation, achieve combination therapy, and reverse immune suppression within the tumor microenvironment.
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校內:2029-08-21公開