乳腺癌佔所有癌症的 11.7％，並且導致癌症死亡總數 6.9％，仍是全世界女性中最常被診斷出的癌症和癌症死亡的主要原因。病患最常接受放射治療，但是高劑量放射線會導致嚴重的副作用。此外，三陰性乳腺癌標準治療方法為化療，但是約 80％患者沒有產生完整療效。因此，近期研究提出放射動力療法進行改善。本研究的目的為設計一氧化碳奈米藥物傳遞系統，並將其合併放射線，利用放射動力的方式釋放一氧化碳進行癌症治療，最後進一步了解一氧化碳對粒線體功能的影響。以具有光電效應的奈米金銀合金作為載體材料，並在奈米金銀合金上裝載一氧化碳釋放分子五羰基鐵(Iron pentacarbonyl, Fe(CO)5)，由放射線照射活化後釋放一氧化碳至組織和細胞中。使用 MTT 選擇生物安全性較高的奈米載體材料；使用肌紅蛋白測定法選擇一氧化碳產生較多的奈米藥物；使用穿透式電子顯微鏡等儀器觀察一氧化碳奈米藥物傳遞系統的物化特性。在動物實驗中，以原位人源腫瘤異種移植動物模型(Patient derived tumor xenograft model, PDX model)，在重度免疫不全小鼠乳脂墊中原位植入人源性乳腺癌腫瘤組織，確認一氧化碳奈米藥物傳遞系統進行放射動力癌症治療之效力。在細胞實驗中，利用人類乳腺癌細胞 MDA-MB-231 進行相關分析，使用台盼藍(Trypan blue)計算細胞存活率；使用螢光染色分析粒線體中活性氧(mtROS)及膜電位的變化，以及自噬作用的改變；使用西方墨點法分析蛋白表達的調控。結果顯示成功合成一氧化碳奈米藥物傳遞系統，並可經由放射線活化釋放一氧化碳，在動物活體中原位人源乳腺癌腫瘤生長被抑制。在細胞中使粒線體中 mtROS 上升、膜電位下降，粒線體功能異常，導致乳腺癌細胞存活率降低，達成癌症治療效果。除此之外，粒線體功能被影響後，相關蛋白如：粒線體中 DRP1 與瓦氏效應(Warburg effect)中PGK1、PKM2、LDHB、細胞凋亡中 Bcl-2 以及自噬作用中 Beclin 1、LC3 表達下降，粒線體中 PDK1 與細胞凋亡Bax、Cytochrome C、Caspase 3 則表達上升。研究證明一氧化碳奈米藥物傳遞系統合併放射線照射後，釋放的一氧化碳影響粒線體功能並調控相關細胞內分子機轉，藉由放射動力方法達到抗癌且專一性的協同功效。同時因應目前個人化精準醫療趨勢，建立人源腫瘤異種移植模型，用以進行合併療法的體內驗證。

In this study, successfully synthesized the carbon monoxide nano-drug delivery system, a biosafety gold-silver alloy as a nano-carrier material containing iron pentacarbonyl (Fe(CO)5). The carbon monoxide nano-drug delivery system is activated by radiation, the energy of radiation destroys the structure of the drug, then releases carbon monoxide into cells and tissues to achieve synergetic radiodynamic cancer treatment. In the tumor microenvironment, significant tumor cytotoxicity improves anti-cancer efficacy and specific synergy effect. Combining carbon monoxide and radiation to perform synergetic cancer treatment, and clarified that carbon monoxide affects mitochondrial function and inhibits the Warburg effect, causing apoptosis and autophagy, which in turn leads to the death of cancer cells. The orthotopic PDX model evaluates the efficacy of carbon monoxide nano-drug combined with radiation for radiodynamic cancer therapy, laying the foundation for the development of clinical evaluation in the future, and promoting the research of precise personalized medicine.

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