Ligand engineering boosts catalase-like activity of gold nanoclusters for cascade reactions combined with glucose oxidase in ZIF-8 matrix

Background: 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. Results: 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 framework8 (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 GOxAu25(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. Significance: 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.