Dextran based dynamic crosslinking nanogel for dual-acid-responsive NO delivery and eradication of S. mutans biofilms

Enzyme-mediated bacterial active endocytosis enhanced the permeability of NG/NO to biofilms. • The chemical structures of Schiff base and NONOates provided dual proton-responsive of gas release. • NO induces S-nitrosylation of PDEs in S. mutans 。, thereby reducing lactate production. Dental caries in permanent teeth have remained one of the most prevalent oral diseases over the past three decades, with their global incidence exhibiting a steady upward trajectory. Streptococcus mutans ( S. mutans ) colonization on dental surfaces, coupled with its acidogenic metabolic activity, constitutes a primary etiological factor in caries pathogenesis. In this work, a NO-loaded polysaccharide nanogel, NG/NO was developed to address this issue. Dextran component of the NG/NO demonstrated selective targeting capabilities, promoting active internalization by S. mutans through enzyme-mediated endocytosis. This mechanism significantly enhanced biofilm penetration of the NG/NO (>70% biofilm penetration depth) within a 4-h exposure. The Schiff base bonds and N-diazeniumdiolates conferred the dual-acid-responsive NO release kinetics, achieving mM concentration of NO liberation within several minutes under cariogenic conditions (pH 4.5–5.5), thereby triggering rapid biofilm disrupting (>80% biomass reduction). Moreover, lower concentration of NO was shown to inhibit glycolysis and synthesis of lactic acid in S. mutans , thus improving acidic environment and demonstrating the potential to prevent enamel demineralization and dental caries. In conclusion, the NG/NO has promising applications in daily oral hygiene maintenance and caries prevention.