本研究使用水果萃取液合成奈米金粒子(gold nanoparticles)，此一新式製程中不需使用有機溶劑，可降低因溶劑殘留而可能產生的細胞毒性。由穿透式電子顯微鏡結果顯示，在不同的反應條件下可以分別合成球型與三角形兩種型態的奈米金粒子，由動態光散射粒徑分析儀的檢測結果指出，球型與三角形奈米金粒子在液相中之平均粒徑分別為46±0.5 nm及66±1.4 nm。
體外細胞實驗中，我們觀察骨母細胞(7F2)對奈米金粒子的攝入情形，TEM影像指出骨母細胞在24小時內便可將奈米金粒子攝入，且隨著時間逐漸往細胞核移動。整體而言，球型奈米金粒子進到細胞所需的時間較短，粒子被細胞排出的速度也比較快，三角形奈米金粒子進到細胞核裡的速率較慢，且粒子在細胞裡的滯留時間較久。
細胞活性的實驗結果指出奈米金粒子在初期並不會顯著地影響細胞活性，但粒子在細胞內滯留超過七天後，細胞活性便開始明顯地被抑制了，與細胞攝入的結果相較，可發現三角形奈米金粒子在細胞裡的滯留時間較久，而使得細胞活性受到抑制。此外，奈米金粒子一旦進入到細胞核裡，便會抑制鹼性磷酸酶的分泌，代表骨細胞的初期分化受到了奈米金粒子的抑制，且與活性變化的趨勢相仿，抑制效應隨著奈米金於細胞核中的滯留時間與濃度增加而越明顯。然而，奈米金粒子對於後期骨細胞的礦化並不會產生影響。
表面增強拉曼光譜監測活細胞之實驗結果顯示，奈米金粒子對細胞的拉曼訊號或有增強的效應，但相對地，細胞的螢光訊號也隨著大幅增強而遮蔽了有意義的拉曼訊號。

In this research, gold nanoparticles (GNPs) with different morphologies were synthesized by using apple extract without any organic solvents. The transmission electron microscopy (TEM) results indicated there were two different shapes of GNPs, spherical and triangle ones. The average sizes of GNPs determined by dynamic light scattering (DLS) were respectively 46±0.5 nm and 66±1.4 nm for spherical and triangle GNPs.
The cellular uptake of GNPs in osteoblast (7F2) was observed by TEM. The result indicated that the GNPs were internalized by cell within 24 hours, and GNPs were gradually approached the nucleus with longer incubation time. The uptake of spherical GNPs took place in shorter period, but spherical GNPs were appeared to exocytose at a faster rate. Triangle GNPs were transported into the nucleus at a slower rate, and the retention time of triangle GNPs in cells was longer than that of spherical GNPs.
In the culture from 1 to 5 day, the uptake of GNPs, no matter spherical or triangle ones, did not affect the viability of osteoblastic cells. However, triangle GNPs suppressed cell activity at the 7th day in the culture, which was possibly because of the long retention time of triangle GNPs in cells. The alkaline phosphatase (ALP) activity of osteoblasts decreased when GNPs appeared in the nucleus. Besides, the inhibition in early osteogenic differentiation was more significant with longer retention time of GNPs in nucleus and higher concentration of GNPs. On the contrary, the biomineralization, the most important marker in the late stage of osteogenic differentiation, was not affected by GNPs.
The results from surface enhance Raman scattering (SERS) show that Raman signals of living cells would be enhanced by internalized GNPs, but the cellular fluorescence was also enhanced dramatically. Therefore, the characterization of osteogenic differentiation by SERS was not successful in this research, which would be enhanced by applying different wavelength in SERS analysis. On the other hand, the expression and decay of ALP was revealed from Raman spectra, revealing the potential of SERS in monitoring osteogenic differentiation.

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