A zinc-iron nanozyme with pH-dependent multi-enzymatic activities for sequential infection control and inflammation resolution in vital pulp therapy.

Vital pulp therapy for caries-induced pulpitis is limited by the acidic, oxidative and inflammatory microenvironment. Here, we present zinc-iron nanozymes (ZFNs) designed for sequential infection control and inflammation resolution. ZFNs exhibit pH-dependent multi-enzymatic activities: optimal peroxidase-like activity at pH 5.0 (mimicking the Streptococcus mutans microenvironment) and dominant catalase- and superoxide dismutase-like activities at neutral pH. Under acidic conditions, ZFNs convert H2O2 into hydroxyl radicals, achieving >99% bactericidal efficacy against S. mutans and suppressing bacterial acid production. At neutral pH, ZFNs scavenge reactive oxygen species, reduce intracellular reactive oxygen species levels in inflamed dental pulp stem cells, and downregulate pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and IL-8). They also partially restore osteogenic/odontogenic differentiation markers (ALP, RUNX2, and DSPP). In a rat pulpitis model, direct pulp capping with ZFNs substantially decreased pulpal necrosis and inflammatory infiltration on day 5 and promoted tissue repair, showing early anti-inflammatory effects comparable to or better than the commonly used clinical material iRoot BP. These findings suggest that this nanozyme platform with pH-dependent multi-enzymatic activities can support sequential infection control and inflammation resolution, offering a potential strategy for vital pulp therapy.