癌症仍是全球主要死因之一，而現有治療方式如手術、化療與放療常伴隨副作用大、復發率高等問題。因此，開發具選擇性且高效的治療策略成為當前研究的重要方向。腫瘤微環境中葡萄糖代謝旺盛，且富含內源性過氧化氫 (H2O2) 與氯離子 (Cl⁻)，為催化治療提供了理想條件。基於此，本研究旨在設計一種能精準利用腫瘤內源代謝物，並促進協同催化以增強ROS與RHS產生的創新治療策略。
我們開發了一種基於共價有機框架 (Covalent Organic Frameworks, COFs) 的創新催化治療平台，透過伽凡尼置換反應 (Galvanic replacement reaction) 以及乙醇還原法，將金 (Au) 與銥 (Ir) 原子整合於COF骨架中，構築出COF/Aux/Ir1–x雙原子催化系統，並於表面包覆透明質酸 (Hyaluronic acid, HA) 以提升其生物相容性及靶向性。
此雙金屬單原子結構 (COF/Au0.75/Ir0.25 NPs) 可促進高效的協同催化循環，有效促進葡萄糖氧化與活性氧物種 (Reactive Oxygen Species, ROS) 及活性鹵素物種 (Reactive Halogen Species, RHS) 的產生，其中Au催化葡萄糖氧化生成葡萄糖酸與過氧化氫 (H2O2)，而Ir則負責將 H2O2 分解為超氧陰離子 (Superoxide, O2•⁻)，並於氯離子 (Cl⁻) 存在下產生次氯酸 (HOCl)。雙原子催化位點進一步驅動正回饋循環，使H2O2 持續轉化為氧氣 (O2)，使氧氣再次回到Au催化葡萄糖氧化的過程，增加後續ROS 與 RHS 在腫瘤細胞內的累積，顯著提升催化治療的效率。
最後在細胞實驗與動物模型中，COF/Au0.75/Ir0.25 NPs 不僅顯示出卓越的腫瘤抑制效果，亦對主要正常器官無明顯毒性損害，展現良好的生物相容性與安全性。綜合上述成果，本研究成功建立一種由腫瘤內源性代謝物驅動，具高度選擇性與治療效率的協同腫瘤治療策略。

A novel catalytic therapy platform based on Covalent Organic Frameworks (COFs) with dual-atom metal sites is developed to enhance selectivity and efficiency in cancer treatment. Leveraging the tumor microenvironment—rich in glucose, hydrogen peroxide (H2O2), and chloride ions (Cl⁻)—the system enables synergistic catalysis to boost reactive oxygen species (ROS) and reactive halogen species (RHS) generation. Gold (Au) and iridium (Ir) atoms are incorporated into the COF framework via galvanic replacement, forming COF/Aux/Ir1–x dual-atom catalysts. To improve biocompatibility and tumor targeting, the surface is further coated with hyaluronic acid (HA), which recognizes CD44 receptors overexpressed on cancer cells. In this system, Au catalyzes glucose oxidation to generate gluconic acid and H2O2, while Ir decomposes H2O2 into superoxide (O2•⁻) and produces hypochlorous acid (HOCl) in the presence of Cl⁻. Dual-atom catalytic sites initiate a positive feedback loop, continuously converting H2O2 into oxygen (O2), accelerating ROS and RHS accumulation in tumor cells. By fine-tuning the Au:Ir ratio, optimal catalytic performance and therapeutic efficiency are achieved. This strategy offers a selective, metabolism-driven approach for effective cancer treatment.

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