本研究使用葉酸做為還原劑及封端劑，以加熱法一步驟合成出葉酸-奈米金粒子，並且透過不同的葉酸濃度來控制葉酸-奈米金粒子的形狀，分別合成球形與非球形兩種型態的葉酸-奈米金粒子，球形與非球形葉酸-奈米金粒子粒徑分別為43.3±12.5 nm及46.5±6.2 nm。葉酸-奈米金粒子具有良好的穩定性，其介達電位能持續保持在-6 mV以及-8 mV長達30天以上。
在細胞攝入實驗中，我們觀察了骨癌細胞(UMR)與骨母細胞(7F2)對於葉酸-奈米金的攝入機制，細胞切片的TEM影像顯示，在1天後便可將葉酸-奈米金粒子攝入，在攝入3天後細胞質內葉酸-奈米金含量達最高峰，在3至7天時行胞吐作用排出，除此之外，由於骨癌細胞有葉酸受體表現，導致骨癌細胞攝入的含量相較於骨母細胞更多，且球形葉酸-奈米金粒子攝入骨細胞內的含量也比非球形葉酸-奈米金粒子多。
在體外細胞實驗部分發現，30 μM的葉酸-奈米金會影響分化，促進鹼性磷酸酶的分泌以及鈣鹽的沉積；而葉酸-奈米金濃度若在20 μM以下則不會對細胞活性、細胞分化、蛋白質分泌以及礦化造成影響。
表面增強拉曼光譜結果顯示，葉酸-奈米金粒子對細胞的拉曼訊號有增強的效應，由於非球形葉酸-奈米金粒子具有尖銳邊緣可增強周邊電場，與球形葉酸-奈米金粒子相比有更強的拉曼訊號，此外，葉酸-奈米金對骨癌細胞中的拉曼訊號表現出較佳的增強效果，這是因為癌細胞對葉酸-奈米金粒子具有更高的攝入量。

In this research, folic acid (FA) was used as a reducing and capping agent to synthesize gold nanoparticles (GNPs) in a one-step process. The shapes of FA-GNPs were controlled by different folic acid concentrations and spherical FA-GNPs and non-spherical FA-GNPs were synthesized respectively. The particle size of spherical FA-GNPs and non-spherical FA-GNPs were 43.3±12.5 nm and 46.5±6.2 nm, respectively. FA-GNPs have good stability, and their zeta potential were maintained at -6 mV and -8 mV for more than 30 days.
UMR (Rat osteogenic sarcoma) and 7F2 (Osteoblast) cells were used to identify the cellular uptake of FA-GNPs. From TEM images, the cellular uptake for FA-GNPs took about 1 day, and the maximum number of FA-GNPs in cytoplasm was reached after 3 days. After the culture for 3-7 days, the exocytosis of GNPs was observed. The uptake of GNPs in UMR cells was higher than that in 7F2 cells due to the abundant folate receptor on the surface of UMR cells. Besides, the uptake of spherical FA-GNPs was much higher than non-spherical FA-GNPs.
According to in vitro tests, it was found if the FA-GNPs concentration was less than 30 μM, the cell viability, differentiation, protein secretion, and mineralization were not affected. On the other hand, FA-GNPs which was more concentrated than 30 μM would enhance the cell viability and mineralization. No matter for UMR or 7F2 cells in this study, the limit of 30 μM for the non-osteoconductivity of GNPs.
The results from surface enhanced Raman spectroscopy (SERS) indicated that the FA-GNPs enhanced the intensity of the Raman spectra significantly. The non-spherical FA-GNPs showed a better enhancement in Raman spectroscopy than the spherical ones. This was because the sharp edges of non-spherical GNPs promoted surrounding electric field. In addition, the Raman signals from UMR were enhanced more than 7F2, which was caused by the higher cellular uptake of FA-GNPs in the cells with folate receptors.

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