Surface-Engineered pH-Responsive Cobalt Sulfide Nanozyme for Caries Therapy

Dental caries is driven by acidogenic biofilms embedded in an extracellular polymeric substance matrix, which shelters inner bacteria and diminishes antimicrobial efficacy. Nanozyme-based catalytic therapy is a promising alternative, whereas the inadequate catalytic performance coupled with weak interaction with bacteria severely limits the therapeutic efficacy. In this study, a pH-responsive polyethyleneimine-engineered cobalt sulfide (PCoS) nanozyme with a positive charge was developed, exhibiting enhanced oxidase- and peroxidase-like dual activities that were selectively initiated under acidic conditions. PCoS nanozyme effectively adsorbed onto bacterial surfaces, killed planktonic Streptococcus mutans, and disrupted mature biofilms by damaging bacterial membranes and reducing extracellular polymeric substance accumulation. Transcriptomic analysis further revealed alterations in metabolic pathways, suggesting that PCoS-mediated oxidative damage resulted in structural injury and bacterial physiology impairment. In a rat caries model, the dual enzyme-like activities of PCoS significantly reduced smooth and sulcal surface caries severity, preserved enamel structure by selectively suppressing cariogenic taxa, and maintained overall oral microbial diversity. These findings demonstrate that PCoS functions as a pH-responsive dual enzyme-like nanozyme that selectively disrupts cariogenic biofilms and prevents caries progression while preserving oral microbial homeostasis, supporting its potential for ecological caries management.