逆微胞輔助之球狀石墨烯複合材料合成 於光動力治療之應用

Abstract

石墨烯，此一前瞻性的材料，在許多領域上均有突破性的發展，並且也已逐步被研究並應用於藥物釋放系統，期望可做為癌症診斷治療的新劑型。然而雖然石墨烯的二維結構已知能吸附大量的小分子化合物作為藥物傳遞的載台，但目前其材料大小型態仍不易控制，由於其異相維狀結構的關係，細胞對於此類材料的攝取效率也差異極大，並非一個良好的載具。因此本研究在溫和的條件下自組裝合成球狀的石墨烯，期望保有石墨烯原有的特性並增加細胞吞噬性。利用可產生單一態氧1O2 (singlet oxygen) 的亞甲藍分子作為光動力治療的模型，進行毒殺癌細胞的評估。研究結果顯示所開發的球狀石墨烯與傳統二維石墨烯比較，細胞吞噬效率為原來的3倍(30 % vs. 10 %)，由此可降低所需使用的光源功率與照射時程 (2mW, 1.5 min) 便足以促使癌細胞的光毒殺效率加倍( 60 % vs. 30 %)，使球狀石墨烯具有極大潛力作為未來光動力治療的新穎載具材料。

The graphene oxide (GO), has created huge breakthrough development in diverse fields. It was also assessed for drug delivery systems and employed as new formulation for cancer theranostics. Although it has been reported that extended conjugated aromatic ring of GO enabled the absorption of large amount of small molecules for drug delivery vehicles, the size and geometry control was challenging and the agglomeration occurred frequently. Owing to its anisomerous dimensions, the uptake efficiency of cells varies and was not optimized. Herein, we developed a method to enable self-assembly of reduced graphene oxide nanospheres (rGON) under mild condition while the pristine properties of GO were preserved and cellular uptake could be enhanced. Additionally, we employed the methylene blue, a photosensitizer, which could generate singlet oxygen (1O2) in the rGON for photodynamic treatment of cancer cells. Comparing with conventional 2D graphene oxide, 3 folds higher cellular uptake (30 % vs. 10 %) enabled low power density (2 mW) and short irradiation time (1.5 min) to double photocytotoxicity of cancer cells (60 % vs. 30 %), indicating great potential of rGON composites to serve as new photodynamic therapeutics in the future.