合成含腺嘌呤核苷之新型奈米碳管

近年來，奈米碳管已經被廣泛的應用在藥物載體方面，相較於傳統經血液循環使藥物分散於身體各器官，它可作為藥物載體投遞藥物至目標細胞或器官中，以避免藥物未到達目標細胞時即被免疫系統給代謝掉，提高藥效，因此實驗室設計一含腺嘌呤核苷衍生物之新型奈米碳管，其可作為辨認DNA序列之高專一性載體，將藥物準確投遞至目標細胞，降低藥物之副作用並提高疾病治癒效果。　　其欲修飾至奈米碳管之腺嘌呤核苷衍生物，為利用3''-O-[(tert-butyl)-di-methylsilyl]-2''-deoxyadenosine (14)與9-azido-4,7-dioxanonanoic acid (7)進行酯化反應，得到具有azide官能基之5''-O-(9-azido-4,7-dioxanonanyl)-2''-deoxy-adenosine (16)。另一方面我們利用p-amino phenyl propargyl ether (19)進行官能基化修飾三鍵基團於奈米碳管上，接著藉由Click化學反應，使其具有azide官能基之腺嘌呤與奈米碳管上之三鍵進行銜接，合成含腺嘌呤核苷衍生物之新型奈米碳管 (2)。　　並藉由紅外線光譜儀、拉曼散射儀器、熱重量損失分析儀及高解析掃描穿透式電子顯微鏡證實已成功得到腺嘌呤核苷衍生物之新型奈米碳管，重要的為Click反應產率為77%，相較於先前實驗室之Click產率提升兩倍，更加印證Click反應產率高、簡單且選擇性好，因而得到高效率之腺嘌呤核苷衍生物奈米碳管，此官能基化之奈米碳管即可應用於辨認疾病目標序列，成為高專一性之藥物投遞載體，優點為可接合上辨認不同疾病之DNA特殊序列，治癒更多疾病，並提高治療效果降低副作用，給予病患治療疾病一線生機。

關鍵字

去氧核醣核酸；奈米碳管；藥物載體；腺嘌呤核苷

並列摘要

Carbon nanotubes with their unique pseudo-one-dimensional nanostructures and related electronic, optical, and mechanical properties have been attracting much attention for potential biological applications, such as biosensors, bio-delivery, bio imaging and so on. Recently, carbon nanotubes have been explored as multipurpose innovative carriers for drug delivery and diagnostic applications. In this thesis, recent studies and advances toward bioapplications of carbon nanotubes are reviewed, followed by detailed reports on my research project concerning the use of stable complexes between carbon nanotubes and DNA for gene therapeutic capacity are mentioned. 　　In our project, we used 3''-O-[(tert-butyl)dimethylsilyl]-2''-deoxyadenosine (14) and 9-azido-4,7-dioxanonanoic acid (7) as our starting materials. The reaction with the adenosine derivative gave 5''-O-(9-azido-4,7-dioxanonanyl)-2''-deoxyadenosine (16). After that we successfully functionalized the carbon nanotubes by using the p-amino phenyl propargyl ether (19). Finally the functionalized carbon nanotube derivative (1) coupled with 5''-O-(9-azido-4,7-dioxanonanyl)-2''-deoxyadenosine (16) by using click reaction results multi-adenosine derivatives on to carbon nanotubes (2). 　　Then we used infrared spectroscopy, Raman spectra, thermogravimetric analysis spectra and HRSTEM spectra to confirm wrapping of multi-adenosine derivatives on to carbon nanotubes. Importantly, when we compared to previous data that the click reaction yield is enhanced to 77%. It indicates that the click reaction is simple and good selectivity with high efficiency. The functionalised carbon nanotubes has high specificity in drug delivery and targetting DNA sequence. The functionalised carbon nanotubes has the advantage to cure the diseases in efficient way with less side effects.

並列關鍵字

Adenosines ； DNA ； drug delivery ； carbon nanotubes

參考文獻

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18. Yang, S. –T.; Fernando, K. A. S.; Liu, J. –H.; Wang, J.; Sun, H. –F.; Liu, Y.; Chen, M.; Huang, Y.; Wang, X.; Wang, H.; Sun, Y. –P. Covalently PEGylated Carbon Nanotubes with Stealth Character In Vivo. Small 2008, 4, 940–944.

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3. Iijima, S. Single-shell carbon nanotubes of 1-nm diameter. Nature 1993, 363, 603–605.

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合成含腺嘌呤核苷之新型奈米碳管

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