結合化療與光熱療法之大腸直腸癌奈米藥物載體開發

The development of nano-carrier for colorectal cancer by the combination of chemotherapy and photothermal therapy

黃筱婷(Hsiao-Ting Huang)

指導教授 ： 謝銘鈞

國立臺灣大學/工學院/醫學工程學研究所/碩士(2020年)

https://doi.org/10.6342/NTU201904460

摘要

大腸直腸癌目前已是全球人類死亡的重大疾病之一，而國內隨著經濟進步、飲食習慣西方化，大腸直腸癌的發生率隨之增加，約有三分之一的大腸直腸癌患者於診斷時即已發生轉移，轉移性大腸直腸癌無法使用手術切除，因此治療以全身性化學治療為主。而本計畫即是利用人類血清白蛋白 (Human serum albumin, HSA) 分子所帶有的疏水官能基將化療藥物7-乙基-10-羥基喜樹鹼 (7-Ethyl-10-hydroxycamptothecin, SN-38) 包覆於內，接著HSA會與polyetherimide (PEI) 混合，以利於金還原於奈米粒子表面，最後在此藥物載體表面還原奈米金團簇用以作為大腸直腸癌光熱治療之有效藥物載體。其中，HSA可增加此奈米藥物載體於血液中之相容性，有效增加此奈米藥物載體在血液中的半衰期，提高整體治療效果與降低化療藥物的毒性。而表面還原之奈米金團簇可藉由近紅外光的照射產生高溫，同時此高溫也可促進腫瘤細胞對化療藥物之敏感性甚至直接殺死腫瘤細胞。故此奈米藥物載體結合化學療法與光熱療法，提高化療藥物於血液之半衰期、降低病患之副作用與提高大腸直腸癌治療之效果。

關鍵字

大腸直腸癌 ； 人類血清白蛋白 ； 化學治療 ； 光熱治療 ； 奈米金 ； 7-乙基-10-羥基喜樹鹼

並列摘要

Colorectal cancer is one of the main causes of death worldwide, and is currently undergoing a rapid increase in incidence. About a third of colorectal cancer patients have cancer metastasis at the time of diagnosis. In this study, the 7-Ethyl-10-hydroxycamptothecin (SN-38) molecules could be loaded in human serum albumin (HSA) nanoparticles by the hydrophobic side groups of amino acid in HSA. And HSA mixed with polyetherimide (PEI) could offer reduction sites for HAuCl4 to forming gold nanoclusters on the surface easily. Then, the gold nanocluster could be reduced and aggregated on the surface of SN-38-loaded nanoparticles (HSA/SN-38/PEI NPs) to obtain NIR-absorbent plasmonic nano-carriers (HSA/SN-38/PEI@Au NPs) for chemotherapy and photothermal therapy. When NIR irradiation, the local regional heat can promote the sensitivity of tumor cells to chemotherapy drugs and even directly kill the tumor cells. Finally, the use of this nano-carrier could improve the half-life of chemotherapy drugs in the blood and reduce the side effect, and is significantly more efficacious than the chemotherapy or photothermal therapy alone for colorectal cancer therapy.

並列關鍵字

colorectal cancer ； human serum albumin ； chemotherapy ； photothermal therapy ； gold nanocluster ； 7-Ethyl-10-hydroxycamptothecin (SN-38)

參考文獻

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