Multifunctional drug in drug nano-assembly with antibiofilm and remineralization for preventing dental caries

Dental caries remains a widespread oral health concern and presents a significant clinical challenge. Despite ongoing research advancements, current treatment strategies often fall short of simultaneously addressing several critical factors—namely, effective removal of cariogenic biofilm, promotion of enamel remineralization, preservation of the oral microecological balance, and avoidance of cytotoxic residues within the repair layer. Herein, we developed a multifunctional ''drug-in-drug'' nano-assembly (TA-BBR-ACP) by integrating natural phytochemicals—tannic acid (TA) and berberine (BBR)—as anti-biofilm agents and targeting carriers, with amorphous calcium phosphate (ACP) serving as the remineralization component. The TA-BBR-ACP assembly exhibits significantly anti Streptococcus mutans biofilm activity both in vitro and in vivo. Meanwhile, it enhances ACP efficacy in promoting enamel remineralization and occluding exposed dentinal tubules, without leaving residual matter. In the dental caries rat model, TA-BBR-ACP demonstrates excellent ability to prevent dental caries and maintain oral microbiota homeostasis.