癌細胞球團內細胞滅亡效率與攝入金奈米顆粒與光敏劑濃度之關係研究

Dependence of Cancer Cell Damage Efficiency on Up-taken Gold Nanoparticle and Photosensitizer Concentrations in a Cell Spheroid

劉明俊(Meng Chun Low)

指導教授 ： 楊志忠

國立臺灣大學/電機資訊學院/光電工程學研究所/碩士(2018年)

https://doi.org/10.6342/NTU201802259

摘要

在此論文中，我們以不同濃度的光敏劑磺化鋁酞菁（AlPcS）和接上光敏劑的金奈米顆粒（GNP-AlPcS）及金奈米棒（GNR-AlPcS）孵育細胞球團，並研究細胞球團在雷射照射後其受損細胞的增加趨勢。我們發現在以AlPcS孵育的情況下，隨著AlPcS濃度的上升，在660 nm雷射照射後受損細胞增加的比例呈現先快速上升再緩慢增加的趨勢。以GNP-AlPcS孵育時，在雷射照射後受損細胞的變化是先增加後減少。若是在細胞球團形成後再孵育GNP-AlPcS，受損細胞的數量則是隨金奈米顆粒濃度的增加而增加。於細胞球團形成前以金奈米棒（GNR）孵育，在雷射照射後其受損細胞呈遞增趨勢。然而，若在細胞球團形成前以GNR-AlPcS孵育，照射雷射後受損細胞增加的比例是先增加後減少。另一方面，於細胞球團形成後以GNR孵育，在雷射照射後其受損細胞的增加趨勢是先上升後飽和。若是在細胞球團形成後再孵育GNR-AlPcS，照射雷射後其受損細胞以超線性的趨勢增加。簡單來說，這結果歸因於在高濃度下較淺的雷射穿透深度，導致較小範圍的細胞受到損傷，即使是更高濃度的AlPcS，GNP-AlPcS和GNR-AlPcS可以更有效地損害細胞。對於沒有接上AlPcS的GNR，由於其吸收較小，在雷射照射後細胞損傷的效率是呈遞增趨勢。在細胞球團形成後再以GNP-AlPcS，GNR或GNR-AlPcS孵育，因為只有表面的細胞會吞噬奈米顆粒，所以光熱作用只對表面的細胞有殺傷力，而部分光敏劑因為脫離金奈米顆粒並滲入內層的細胞，所以光動力療法對內層的細胞亦有效果。

關鍵字

癌細胞球團 ； 金奈米顆粒 ； 光敏劑 ； 光熱療法 ； 光動力療法

並列摘要

The dependence of increased damaged cell percentage in a cancer cell spheroid upon laser illumination on the incubated concentration of photosensitizer, AlPcS, gold nanoparticle (GNP), or gold nanorod (GNR) linked with AlPcS, i.e., GNP-AlPcS or GNR-AlPcS, is demonstrated. It is discovered that with AlPcS incubation, the increment of damaged cell percentage upon 660-nm laser illumination increases first fast and then slowly with AlPcS concentration. With GNP-AlPcS incubation, the increment of damaged cell percentage upon laser illumination increases first and then decreases. If GNP-AlPcS are incubated after the spheroid is formed, damaged cell percentage increases with increasing concentration of nanoparticle. With gold nanorod (GNR) incubation before cell spheroids are formed, the increment of damaged cell percentage upon laser illumination increases monotonically. However, with GNR-AlPcS incubation before cell spheroids are formed, the increment of damaged cell percentage upon laser illumination increases first and then decreases. On the other hand, with GNR incubation after the formation of cell spheroids, the increment of damaged cell percentage upon laser illumination increases first and then saturates. In the case of GNR-AlPcS incubation after the formation of cell spheroids, the increment of damaged cell percentage upon laser illumination increases super-linearly. Simply speaking, the results are attributed to the shallower laser penetration into a cell spheroid and hence cell damage in a smaller volume when the incubated AlPcS, GNP-AlPcS, or GNR-AlPcS has a high concentration even though a high concentration can more effectively damage cells. Without AlPcS linkage onto GNR, because the absorption becomes smaller, cell damage efficiency upon laser illumination can increase with GNR concentration. With GNP-AlPcS, GNR, or GNR-AlPcS incubation after the formation of cell spheroids, photothermal effect is only effective on the surface cells which uptake nanoparticles. Because some photosensitizers are detached from gold nanoparticles and penetrate deeper into the inner cells, photodynamic therapy is also effective for the inner cells.

並列關鍵字

cell spheroid ； gold nanoparticle ； photosensitizer ； photothermal therapy ； photodynamic therapy

參考文獻

[1] T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan, and Q. Peng, “Photodynamic Therapy,” J. Natl. Cancer Inst. 90(12), 889-905 (1998).

[2] D. E. J. G. J. Dolmans, D. Fukumura, and R. K. Jain, “Photodynamic therapy for cancer,” Nat. Rev. Cancer 3(5), 380-387 (2003).

[3] B. W. Henderson, and T. J. Dougherty, “How does Photodynamic Therapy Work?,” Photochem. Photobiol. 55(1), 145-157 (1992).

[4] A. Juarranz, P. Jaen, F. Sanz-Rodriguez, J. Cuevas, and S. Gonzalez, “Photodynamic therapy of cancer. Basic principles and applications,” Clin. Transl. Oncol. 10(3). 148-154 (2008).

[5] I. Yoon, J. Z. Li, and Y. K. Shim, “Advance in Photosensitizers and Light Delivery for Photodynamic Therapy,” Clin. Endosc. 46(1), 7-23 (2013).