本研究利用多孔性二氧化錳奈米殼層包覆氧化鉍奈米核球，搭載化療藥物 Vorinostat (suberoylanilide hydroxamic acid, SAHA)，表層再修飾上 mouse serum albumin (MSA) 及 apo-transferrin (Tf)，形成最終奈米藥物用以治療大腸癌，利用其對癌細胞具有靶向性及多響應性進行化學/化學動力治療，以增強療效並減少對一般組織的副作用。因 Tf 的標靶性，奈米藥物可以有效地被細胞攝入，而所製備的奈米藥物中，二氧化錳可以於細胞中引發 fenton-like reactions，產生具有毒性的活性氧物質 (ROS)，達到化學動力治療的效果，在此同時，受到癌細胞及腫瘤微環境中酸性、高濃度過氧化氫 (H2O2)、高濃度穀胱甘肽 (GSH) 的影響，二氧化錳會降解並釋放出搭載的化療藥物 SAHA，也產生了氧氣，減緩缺氧情形。而 SAHA 能夠以釋放細胞色素c (cytochrome c) 為特徵的線粒體介導的死亡途徑來引發細胞死亡和產生 ROS，達到化療的效果。重要的是，氧化鉍奈米核球可以有效降低大腸癌細胞中高濃度硫化氫 (H2S)，防止 fenton-like reactions 產生的 ROS 被 H2S 消耗，進而增強化學動力治療的效果。

In this study, we used bismuth oxide nanospheres with porous manganese dioxide nanoshells coating, loading Vorinostat (suberoylanilide hydroxamic acid, SAHA) which is a chemotherapy drug, and the surface of particle was modified with mouse serum albumin (MSA) and apo-transferrin (Tf). The final nano-drug was used for the treatment of colorectal cancer. The targeting and multi-responsive ability to cancer cells enhanced the chemo/chemodynamic therapy efficacy and reduced the side effects on general tissues. The targeting ability of Tf improved the cellur uptake of nano-drug. The manganese dioxide of the nano-drug triggered fenton-like reactions to generate toxic reactive oxygen species (ROS) for chemodynamic therapy in the cells. At the same time, with the acidity, high concentration of H2O2 and GSH in cancer cells and the tumor microenvironment, manganese dioxide not only degraded and released SAHA, but also produced oxygen to alleviate hypoxic conditions. SAHA can trigger cell death through mitochondria-mediated death pathways characterized by cytochrome c release and the production of reactive oxygen species. Bismuth oxide nanospheres can effectively reduce the high concentration of H2S in colorectal cancer cells, prevent the ROS produced by fenton-like reactions from being consumed by H2S to enhance the effect of chemodynamic therapy.

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