Atomically Modulated WSe2 Clusters with Enhanced Biocatalytic Activity for Acute Liver Injury Management.

Two-dimensional WSe2 has attracted considerable attention owing to its tunable electronic structure and intrinsic catalytic activity. However, the catalytic redox performance of pure WSe2 remains limited by insufficient charge-transfer efficiency and suboptimal catalytic kinetics in complex oxidative environments. Herein, we constructed a series of ultrasmall WSe2 clusters via atomic-level regulation. This strategy could modulate their electronic configuration and enhance their catalytic performance. The resulting approximately 2 nm M-WSe2 (M = Ce, Pt, Fe) clusters exhibited total antioxidant capacity 2.3- to 4.3-fold higher than that of pure WSe2. Their multienzyme-like activity was increased by 2.2- to 44-fold, and they exhibited broad-spectrum free radical scavenging ability. These atomic-level modulated clusters effectively protected hepatocytes from oxidative stress damage and inhibited macrophage inflammatory response. In the acetaminophen-induced acute liver injury model, M-WSe2 significantly alleviated hepatic oxidative damage and restored redox homeostasis, with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels reduced by approximately 73% and 76%, respectively. Notably, these clusters exhibited favorable biosafety. Through atomic-scale design, this study provided a rational strategy for developing high-performance antioxidant clusters for oxidative stress and inflammation-related liver injury.