為了增強藥物傳遞的效果，本實驗以電噴射(electrospraying)製備五胺基酮戊酸(-ALA)-幾丁聚醣奈米粒子。藉由調整不同的操作條件：流率、操作電壓、collector-tip距離、-ALA 濃度，進而製造出直徑最小及直徑分布最窄之奈米粒子。並利用光交聯反應增加奈米粒子的穩定性。在電噴的過程中加入tetraethyleneglycoldiacrylate (TTEGDA) 及 2,2-dimethoxy-2-phenylacetophenone (DMPA)，同時以UV光照射而達到單步驟交聯。光交聯後之五胺基酮戊酸-幾丁聚醣奈米粒子的形狀可在磷酸鹽緩衝溶液中為持至少一天。並在骨母細胞(osteoblast)及骨癌細胞(osteosarcoma)上展現良好的生物相容性。
光交聯後之五胺基酮戊酸-幾丁聚醣奈米粒子可延遲釋放曲線，達到12小時的穩定釋放。由細胞攝入的結果得知，在4小時培養後，325 奈米之五胺基酮戊酸-幾丁聚醣粒子可以被骨癌細胞及骨母細胞吞噬入細胞質中。
由毒性測試的結果指出，五胺基酮戊酸的親水性降低了光動力治療的效率。而以幾丁聚醣包覆五胺基酮戊酸能有效增加骨癌的毒殺效果，並不對骨母細胞及纖維母細胞造成顯著的毒性。

In this research, -aminolevulinic acid (ALA)-chitosan nanoparticles were prepared by electrospraying. The main parameters in electrospraying process, including ALA concentration, applied voltage, flow-rate, and tip-collector distance, were optimized to obtain spherical and mono-dispersed nanoparticles for drug delivery.
To enhance the anti-swelling ability of nanoparticles for the reduction of burst release, chitosan nanoparticles were neutralized with Na2CO3, or photocrosslinked with tetraethyleneglycoldiacrylate (TTEGDA) and 2,2-dimethoxy-2-phenylaceto- phenone (DMPA). With photocrosslinking, the morphologies of chitosan were not changed after immersion in PBS for a day. The processes were diminished into one step by using photocrossking. The treatment was greatly simplified to result in good anti-swelling ability of chitosan nanoparticles, compared with several steps through Na2CO3 neutralization. Besides, photocrosslinked chitosan nanoparticles demonstrated good biocompatibility for osteosarcoma UMR-106 cells and osteoblast 7F2 cells.
From images of confocal fluorescence microscope, the cellular uptake of ALA-chitosan nanoparticles was obvious in UMR-106 and 7F2 cells after the culture for 4 h. With the incubation of 1 and 2 days, the internalization of chitosan particles was still clear in cytoplasm and nucleus of UMR-106 and 7F2 cells. The results support that for chitosan nanoparticles developed in this study, their cellular uptake and duration were efficient in osteogenic cells.
The photodynamic therapy (PDT) efficacy of ALA-chitosan was tested on UMR-106, 7F2 and skin fibroblast L929 cells with the radiation energy of 234 mW/cm2 for 10 minutes. From the cell culture with ALA-chitosan nanoparticles under low-energy irradiation, the cytotoxicity of ALA-chitosan was the highest in UMR-106 cells, and the second highest was in L929 cells. On the other hand, the cytotoxicity of ALA-chitosan was insignificant in 7F2 cells. The results reveal that the PDT efficiency of ALA was greatly promoted by chitosan nanoparticles especially for osteosarcoma cells, supporting the potential of ALA-chitosan nanoparticles in the treatment of bone cancer.

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