Microenvironment-responsive multi-enzyme cascade nanosystem for the treatment of early caries

Abstract

Oral diseases associated with dental biofilms have become one of the frontiers in clinical research due to their complexity. Dental caries is a typical biofilm driven disease resulting from the diet and microbiota-matrix interactions, and it remains a substantial clinical challenge to halt the progression of caries and simultaneously repair the damaged enamel. In this regard, an oral microenvironment-responsive strategy was put forward to develop a multi-enzyme cascade nanosystem possessing antibacterial and in situ mineralization properties. During application in the oral cavity, starch was hydrolyzed by α-amylase, thereby releasing calcium phosphate prenucleation clusters (CaP-PNCs) for in situ remineralization of demineralized enamel, and providing the hydrolysis product glucose. Subsequently, glucose oxidase (GOD) conjugated to dextran-coated iron oxide nanozyme (Dex-IONP-GOD, DIG) catalyzed the production of H₂O₂ from glucose. Under the acidic caries microenvironment, IONP with POD-like activity can trigger H₂O₂ to generate reactive oxygen species. This process exhibited bactericidal activities and effectively inhibited the adhesion and biofilm formation of Streptococcus mutans. This bifunctional multi-enzyme cascade nanosystem accomplishes the adaptive initiation of pathogen elimination and in situ mineralization by its environmental responsiveness, rather than relying on the exogenous substrates, which thus provides a potential strategy for preventing and treating dental caries.