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 Au 25 (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 Au 25 (NAC) 14-17 (MPA) 4-1 exhibited superior CAT-like activity and structural stability than Au 25 (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 (H 2 O 2 ) facilitated by Au 25 (NAC) 14-17 (MPA) 4-1 , and protective function and nanoconfinement effect of zeolitic imidazolate framework-8 (ZIF-8) enabled the GOx-Au 25 (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 H 2 O 2 level after treatment with GOx-Au 25 (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.