Integrating natural enzymes and nanomaterials exhibiting tailored enzyme-like activities is an effective strategy for the application of cascade reactions. It is essential to develop a highly efficient and robust glucose oxidase-catalase (GOx-CAT) cascade system featuring controllable enzyme activity, a reliable supply of oxygen, and improved stability for glucose depletion in cancer starvation therapy. However, the ambiguous relationship between structure and performance, and the difficulty in controlling enzyme-mimic activity, significantly hinder their broader application. Herein, the CAT-like activity of atomically precise Au25(MPA)18 (MPA=3-mercaptopropionic acid) nanoclusters (AuNCs) was modulated by incorporating N-acetyl-l-cysteine (NAC) in a series of ratio. It is found that Au25(NAC)14-17(MPA)4-1 exhibited superior CAT-like activity and structural stability than Au25(MPA)18 owing to the intramolecular hydrogen bond in NAC. Moreover, the synergetic effects of glucose-depletion catalyzed by GOx, oxygen generation from the intermediate hydrogen peroxide (H2O2) facilitated by Au25(NAC)14-17(MPA)4-1, and protective function and nanoconfinement effect of zeolitic imidazolate framework-8 (ZIF-8) enabled the GOx-Au25(NAC)14-17(MPA)4-1@ZIF-8 composite to degrade more glucose. Compared to that treated with a single enzyme or free enzymes, the residual intermediate H2O2 level after treatment with GOx-Au25(NAC)14-17(MPA)4-1@ZIF-8 was about 93% lower than that after treatment with GOx alone. This composite showed higher catalytic activity, stability, and tolerance when applied to GOx-mediated glucose depletion. In brief, the study provides a feasible strategy for realizing robust and efficient cascade reaction by integrating the merits of natural enzymes and atomically precise metal NCs with adjustable enzyme-like activity. This research offers essential guidance for developing a biocompatible and tailored cascade system.
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