新型生物啟發兩性離子多巴胺分子與其抗污及光裂解性能之研究

Novel Bio-Inspired Zwitterion Dopamine Molecule for Anti-Biofouling and Photocleavable Properties

王琳琄(Lin-Chuan Wang)

指導教授 ： 黃俊仁

國立中央大學/工學院/生物醫學工程研究所/碩士(2014年)

摘要

使用合成的生物材料作為血液接觸裝置，通常伴隨著蛋白質，細胞和細菌等大量非特異性吸附。這些最終可能會在臨床醫療上引起不良的致病性問題，如血栓的形成以及生物材料相關的感染問題。在這項研究中，我們採用貽貝啟發的鄰苯二酚衍生物分別為兩性離子多巴胺磺基甜菜鹼（sulfobetaine dopamine, SB-DA）以及兩性離子硝基多巴胺磺基甜菜鹼（sulfobetaine nitrodopamine, SB-nDA）作為二氧化鈦的修飾表面配體，其中，兩性離子硝基多巴胺磺基甜菜鹼（SB-nDA）提供一個光觸發的切換性能。從電化學研究顯示， SB-DA 在 pH3 的環境下具有完全可逆的氧化還原行為，而在 pH 8 環境下是不可逆的。接觸角測角儀和X射線光電子能譜（x-ray photoelectron spectroscopy, XPS）用來了解 pH值置換對於鄰苯二酚衍生物與二氧化鈦基板之間鍵結的變化，以及了解兩性離子硝基多巴胺磺基甜菜鹼（SB-nDA）對於光裂解的構型變化。另外， SB-DA 與 SB-nDA 的防污性能將透過蛋白質和細菌溶液進行驗證。由石英晶體微量天平（quartz crystal microbalance with dissipation, QCM-D）和螢光顯微鏡觀察。試驗表明，透過 pH 置換方法所製備的 SB-DA 薄膜具有最佳抵抗 BSA 和細菌等非特異性吸附的能力。這一發現支持以下論點；透過 pH 值置換製備成高表面密度的兩性離子多巴胺分子自組裝膜，並且首次證明了兩性離子多巴胺分子自組裝的防污性能，其與傳統的硫醇基兩性離子自組裝膜是相媲美的。在此，我們不僅透過一種簡便和有效的辦法製備了兩性離子多巴胺分子自組裝膜，並展示其有效防污性能，也提供深入了解鄰苯二酚衍生物的綁定機制，讓其衍生物能夠充分利用在表面修飾上，另外，也提出一個光觸發分子，其產生表面功能性質的變化，做為可調控分子在納米醫學應用，如標靶分子影像和藥物輸送，具有相當大的發展潛力。

關鍵字

兩性離子 ； 自組裝 ； 光裂解 ； 抗汙

並列摘要

Use of synthetic biomaterials as blood-contacting devices typically accompanies considerable nonspecific adsorption of proteins, cells and bacteria. These may eventually induce adverse pathogenic problems in clinic practices, such as thrombosis and biomaterials-associated infection. An effective surface coating for medical devices has been pursued to repel nonspecific adsorption from surfaces. In this study, we employed mussel-inspired adhesive dopamine molecule with zwitterionic sulfobetaine residue (SB-DA) and catecholic assembly possessing zwitterionic and photocleavable (sulfobetaine nitrodopamine, SB-nDA) as a surface ligand for modification of TiO2. The electrochemical study shows that the SB-DA exhibits fully reversible reduction-oxidation behavior at pH 3, whereas irreversible at pH 8. The contact angle goniometer, and x-ray photoelectron spectroscopy (XPS) were utilized to explore the surface hydration, chemical states and bonding mechanism of SB-DA, indicating that the binding between catecholic hydroxyl group of SB-DA and TiO2 converts from hydrogen bonds to bidentate bonds upon the pH transition from pH 3 to 8. In order to examine the antifouling properties of SB-DA SAMs, the modified substrates were brought to contact with a bovine serum albumin (BSA) solution monitored using a quartz crystal microbalance with dissipation (QCM-D) sensor and bacteria solutions observed under fluorescence optical microscope. The fouling tests show the sample prepared via the pH transition approach enables the resisting of BSA and bacterial nonspecific adsorption to the best extent as the full coverage of SB-DA films. The findings support the pH-modulated assembly of SB-DA in preparation, and for the first time demonstrate the antifouling properties of the SB-DA SAM comparable with traditional thiol-based zwitterionic SAMs. This strategy was applied to the SB-nDA .The success of modification with catechol derivatives opens an avenue to developing a bio-inspired surface chemistry, and allows uses for a wide spectrum of bio-applications. In addition SB-nDA indeed occur in response to light cracking, resulting in changes of functional characters. The application development potential of Nanomedicine

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