合成與評估釔摻雜碳酸鈣作為光敏劑之X光誘導光動力治療在大腸直腸癌的應用

Abstract

結腸直腸癌多年位居國人癌症死因前三位，除了傳統療法，新興療法不斷被開發。其中光動力治療受限於光源穿透深度、光敏感症狀，多數情況僅用於表淺癌症病灶治療。本研究利用 X 光穿透力強的特性，以釔摻雜碳酸鈣作為放射增敏劑，照射 X 光後產生能夠毒殺大腸癌細胞的活性氧族，達到 X 光光動力治療的效果。 以溶液共沉澱法合成釔摻雜碳酸鈣，過程中使用褐藻酸溶液作為分散劑控制粒徑大小，且使其不易團聚，調控 pH 值促成碳酸鈣粒子生成。經由 X 光照射圖譜以及掃描式電子顯微鏡確定材料結晶相、化學組成。釔摻雜碳酸鈣於顯微鏡下呈現 5 微米以內之顆粒大小，且與純碳酸鈣相比出現了形貌變化。 以材料萃取液搭配 L929 細胞進行生物相容性測試，在 WST-1 以及live/dead 兩種試驗下皆展現良好生物相容性；而後以 MC-38 小鼠結腸癌細胞進行體外實驗，與單純低劑量 X 光照射組別相比，添加材料的 X 光光動力組別明顯呈現較低的細胞活性和較高的細胞毒性，在 live/dead 螢光染色觀測也發現 X 光光動力組別有較大面積的結腸癌細胞凋亡。

Colorectal cancer has been among the top three causes of cancer-related deaths, and while conventional therapies remain standard, emerging treatment strategies are continuously being developed. Photodynamic therapy (PDT) is limited by shallow penetration and phototoxicity, making it suitable for superficial lesions mostly. In this study, we utilize the strong penetration ability of X-ray and use yttrium-doped CaCO3 as a radiosensitizer. Upon irradiation, the material generates reactive oxygen species (ROS) capable of killing colon cancer cells, achieving an X-ray activated photodynamic effect. Y-doped CaCO3 was synthesized via co-precipitation method using alginate as a dispersing agent to control particle size and prevent aggregation. The crystalline phase and chemical composition were confirmed by X-ray diffraction and scanning electron microscopy. Y-doped CaCO3 particles were under 5 μm in size and showed morphological changes compared to pure CaCO3. Biocompatibility tests using L929 fibroblasts demonstrated good compatibility in both WST-1 and live/dead assays. In vitro experiment with MC-38 colon cancer cells showed that, compared to the group with low-dose X-ray alone, the X-ray activated Y-doped CaCO3 exhibited significantly lower cell viability and higher cytotoxicity. Live/dead fluorescence imaging also revealed extensive cancer cell apoptosis in the treated group.