| 摘要: | 基因治療是利用生物學方法將目的基因導入患者體內，使之達成目的基因產物，從而使疾病得到治療之療程，而高效的DNA轉染通常需要載體的協助。近年來，利用陽離子雙子型界面活性劑（通過將兩個界面活性劑分子與間隔物連接形成的二聚體狀界面活性劑）製成的奈米載體進行 DNA 轉染一直是科學家研究的熱門主題。然而，與病毒載體相比，這些非病毒載體的效率仍然很低。因此，許多科學家致力於研究影響轉染效率的因素，試圖做出改進。根據文獻，雙子型界面活性劑間隔基若擁有對 pH 的敏感的化學基團，可能提高其轉染效率。另一方面，糖基雙子型界面活性劑因其糖單元的可生物降解性和低細胞毒性而成為了非病毒載體的絕佳選擇之一。在這項研究中，我們合成了具有 N,N′-乙醯乙二胺間隔基的糖基雙子型界面活性劑，並探討其結構隨pH環境差異所產生的變化，進而研究結構對轉染效率影響。在這項研究中，我們發現糖基上的氫氧基與間隔基上的N,N′-乙醯乙二胺基都使整個雙子型界面活性劑的分子的結構，更容易因pH值的改變產生變化，且此界面活性劑能包覆DNA的能力極好，使其能夠達到非常高的轉染效率，因此，此項研究不管是在新材料的應用上，或是研究背後的機制上，必定能在細胞轉染的領域有所幫助。;Gene therapy relies on DNA transfection to repair pathogenic genes, and efficient DNA transfection usually requires the assistance of carriers. DNA transfection by nanocarriers made of cationic gemini surfactants (a dimer-like surfactant formed by linking two surfactant molecules with a spacer) has been a hot topic for years; however, compared to virus-based carriers, the efficiency of these non-viral carriers remains low. Therefore, for the past decade, many scientists have looked into factors that determine the transfection efficiency in an attempt to make improvements. Earlier researches showed that certain chemical groups such as amines on the spacer of gemini surfactants endowed the surfactants with pH-sensitivity and might thereby improve their transfection efficiency. On the other hand, the sugar-based gemini surfactants have been a great choice for non-viral carriers due to the biodegradability and low cytotoxicity of their saccharide units. Accordingly, in this study, we synthesize a sugar-based gemini surfactant with a N,N’-acetylethylenediamine spacer, and explore the changes of its structure with the pH environment, and further study the effect of the structure on the transfection efficiency. In this study, we found that the hydroxyl group on the sugar group and the N,N′-acetylethylenediamine group on the spacer both make the molecular structure of the whole gemini surfactant more susceptible to the variety of pH value, and the ability of this gemini surfactant to form complexes with DNA is excellent, which enabling it to achieve a very high transfection efficiency. Therefore, this research will definitely be helpful for understanding the mechanism behind cell transfection and creating better biomaterial. |
