Saliva-acquired pellicle inspired multifunctional gargle with wet adhesion, photodynamic antimicrobial, and In situ remineralization properties for dental caries prevention

Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries. • We developed a multifunctional gargle solution (CP-SAP), based on a peptide dendrimer nanogel (PDN) modified with saliva-acquired peptide (SAP), serving as an innovative drug delivery carrier with wet adhesion and in situ remineralization properties, capable of efficiently delivering various drugs, including photosensitizers. • CP-SAP's excellent wet adhesion allows it to adhere to the dental surfaces, providing long-lasting therapeutic effects. • CP-SAP demonstrates strong photodynamic antimicrobial efficacy, rapidly eliminating cariogenic bacteria and inhibiting biofilm formation. • PDN and SAP also act as nucleation templates, effectively adsorbing calcium and phosphate ions from saliva to promote rapid remineralization of demineralized dental hard tissues. • In vitro and in vivo studies show that CP-SAP's antibacterial and remineralization effects are comparable to, or superior to, chlorhexidine gargle and fluoride varnish, highlighting its potential in dental caries prevention and treatment.