Yu, SubinSubinYuKang, HaeunHaeunKangJee, SeohyeonSeohyeonJeeMoon, WooYeonWooYeonMoonJang, DohyubDohyubJangHuang, Wen‐TseWen‐TseHuangKim, DongjunDongjunKimChung, KyungwhaKyungwhaChungWon, Dong‐IlDong‐IlWonPark, JungwonJungwonParkLiu, Ru‐ShiRu‐ShiLiuChoi, KyungminKyungminChoiKim, SehoonSehoonKimLee, Luke P.Luke P.LeeKim, Dong HaDong HaKim2025-06-302025-06-302025-05-27https://scholars.lib.ntu.edu.tw/handle/123456789/730369Metal–organic frameworks (MOFs) are widely used as substrates for creating single-atom catalysts due to their abundance of ligands, facilitating enzyme-like activity for biomedical applications. However, the high-temperature calcination process for single-atom catalysts limits economical, efficient, and large-scale synthesis. Here, a simple room-temperature synthesis of MOF-based single-atom and metal cluster catalysts is presented for tumor therapy. Fe/MOF is obtained through a coordination reaction at room temperature, while Au/MOF is synthesized from Au3+/MOF by introducing a reducing agent. Au/MOF effectively generates hydrogen peroxide (H2O2) from glucose, outperforming Au3+/MOF, and Fe/MOF subsequently produced hydroxyl radicals (•OH) by decomposing the generated H2O2via accelerated peroxidase-like activity in an acidic environment. In vitro and in vivo studies confirm a significantly enhanced cancer eradication ability compared to the PBS-treated group by combining cascade enzymatic activity, destruction of oxidative homeostasis, and excessive mitochondrial-mediated lipid peroxidation. The novel synthesis process of MOF-based metal single-atom catalysts establishes a new paradigm for fabricating effective enzyme-like nanomaterials for multimodal tumor therapy.englucose oxidase mimicmetal–organic frameworkperoxidase mimicsingle atom catalysttumor therapy[SDGs]SDG3journal article10.1002/adhm.202501058