儘管目前那些具有抗藥性的病菌感染影響著我們生活，可能使大眾的生活環境惡化，細菌透過長時間抗生素篩選或改變其DNA序列獲得了抗藥性。由於藥物持續從細胞排出及降解使得藥物治療效果比例降低，導致藥物在所需作用部位的有效濃度降低。通過克服藥物的降解速率及持續在特定部位釋放藥物的釋放機制，奈米劑型藥物發展因此獲得了更多的關注。通過合成吸附過氧化氫的不同矽鋁比例中孔洞奈米矽球來克服抗藥性的問題，更進一步利用幾丁聚醣包覆獲得正電荷的Al-MSN-40@H2O2-chit以增加活性氧類的水平。傅里葉轉換紅外光譜、比表面積與孔隙度分析和掃描式電子顯微鏡等分析研究，支持證實我們的配方成功合成高度可調整表面積及良好型態的奈米粒子。除此之外，帶正電荷奈米粒子的細胞吸收研究令人興奮，攜帶正電荷的製劑強烈的吸引帶負電荷的具抗藥性大腸桿菌。另外，通過評估抑菌環研究及抑制DNA合成研究，顯示我們的製劑已產生出巨大的作用，並通過增加細菌細胞內的活性氧類含量來抑制其生長。除此之外，在HT-29癌細胞中毒理學研究，我們的製劑未顯示任何毒性。總體而言，孔洞結構的劑型解決了該問題，並克服了抗藥性細菌感染。

Despite, the antibiotic drug resistance bacterial infections may worsen the live of public now a day. The bacteria obtained resistance by prolong treatment of antibiotics or change their DNA sequence. The drug therapeutic index was reduced by efflux the drug from cell and involve in the degradation process, which leads amount of drug concentration was less at desired action site. The nanomedicine filed of studies gain more attention and overcome drug degradation rate and release drug at specific site with sustained release mechanism. To overcome the drug resistance problem by synthesized different Si/Al ratio of mesoporous silica (MSNs) and loaded with hydrogen peroxide, further coated with chitosan to gain highly positively charged Al-MSN-40@H2O2-chit employed to increased Reactive oxygen species (ROS) levels. The physicochemical characterization studies, like FTIR, BET, and SEM analysis studies support our formulation was successfully synthesized with high tunable surface area and good morphology. Besides that, positive charge carrying nanoparticle cellular uptake studies revels, the highly positively charged formulation has strongly attracted towards negatively charged drug resistant E. coli bacteria. Further, antimicrobial studies were evaluate by zone inhibition studies and DNA synthesis inhibition studies, which attributes our formulation has been shown tremendous effect and inhibit the growth by increased the ROS levels inside bacterial cells. In addition, toxicological studies were conducted in HT-29 cancer cells, our formulation have not shown any toxicity. Over all, the well architecture formulation was addressed the problem and combat to overcome the drug resistance bacterial infections.

1. 研究目的與動機 1
2. 背景介紹 2
2.1 抗生素 8
2.2 生物膜 10
2.3 過氧化氫 11
2.4 奈米材料 (Nanomaterials) 12
2.5 中孔洞奈米矽球 (Mesoporous silica nanoparticles, MSN) 15
2.6 幾丁聚醣 (Chitosan) 17
3. 實驗方法與材料 18
3.1 化學藥劑來源 18
3.2 細胞及菌株來源和培養 20
3.3 合成Al-MSN 20
3.4 Al-MSN吸附過氧化氫後再包覆幾丁聚醣 21
3.5 場發射掃描式電子顯微鏡 22
3.6 氮氣等溫吸附/脫附量測 (N2 adsorption/desorption isotherm) 23
3.7 雙氧水釋放實驗 25
3.8 定量奈米粒子的過氧化氫吸附量 26
3.9 抗菌活性測試 26
3.10 細胞毒性測試 27
3.11 DNA損害 28
4. 結果 29
4.1 不同矽鋁比的掃描式電子顯微鏡圖 29
4.2 不同矽鋁比的表面積、孔洞體積及孔洞尺寸 30
4.3 不同矽鋁比的FT-IR光譜分析 33
4.4 不同矽鋁比的抗菌能力 35
4.5 固態核磁共振光譜 37
4.6 不同包覆方式的過氧化氫殘留量 38
4.7 不同包覆方式的抗菌效果 40
4.8 包覆前後的表面積、孔洞體積及孔洞尺寸 41
4.9 包覆前後的氮氣吸附脫附分析及孔洞分布情形 42
4.10 包覆幾丁聚醣的FT-IR光譜分析 45
4.11 細胞毒性測試 47
4.12 利用DNA電泳法比較奈米粒子對細菌DNA的損害 48
4.13 Al-MSN-40@H2O2-chit處理後的大腸桿菌SEM分析圖 50
4.14 Al-MSN-40@H2O2-chit處理後的大腸桿菌AFM分析圖 51
4.15 利用螢光顯微鏡觀察奈米粒子與細菌之間的作用 52
4.16 比較Al-MSN-40@H2O2-chit對革蘭氏陽性菌、革蘭氏陰性菌及抗藥菌株的抗菌活性 54
5. 討論 56
6. 結論 65
7. 參考文獻 66

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