Single active Au1O5 clusters for metabolism-inspired sepsis management through immune regulation

Abstract

Artificial enzymes with reprogrammed and augmented catalytic activities hold significant potential in biomedicine. However, common issues with biocatalysts are the presence of numerous inactive site atoms, leading to inefficiencies in their catalytic processes. To leverage the full potential of active catalytic sites, we aim to minimize the biocatalyst structure, transitioning from nanoparticles or polymetallic atomic clusters down to singular-active-unit molecules. In this context, we have developed a unique single active-site cluster molecule, Au₁-O₅-Na₉-(OH)₄ (AuO) clusters, comprising a single gold atom, five oxygen atoms, and a protective layer, where Au-O acts as a singular-active site displaying elevated catalytic activities without inefficiencies associated with biocatalytic reactions. AuO clusters demonstrate activities reminiscent of nicotinamide adenine dinucleotide oxidase (NOX), glutathione peroxidase (GPx), and urease, among other oxidoreductase functions, through optimal utilization of atoms. Clusters are instrumental in enhancing the redox balance, mitigating inflammation, and averting inflammation-induced cellular apoptosis, thereby preserving immune balance in sepsis. These mechanisms are crucial in sepsis pathogenesis. Demonstrating GPx-like and NOX-like capabilities, the AuO clusters have shown remarkable effectiveness against lipopolysaccharide-induced and cecum ligation puncture-induced multiorgan damage, underscoring their substantial promise for sepsis management.