ObjectivesThe objectives of this study were to: (1) develop a multifunctional adhesive via dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP); and (2) investigate its ability to provide metalloproteinases (MMPs) deactivation and remineralization for long-term dentin bonding durability. MethodsDMAHDM and NACP were incorporated into Adper™ Single Bond 2 Adhesive (SB2) at mass fractions of 5% and 20%, respectively. Degree of conversion and contact angle were measured. Endogenous MMP activity of the demineralized dentin beams, Masson’s trichrome staining, nano-indentation, microtensile bond strength and interfacial nanoleakage analyses were investigated after 24 h and 3 months of storage aging in artificial saliva. ResultsAdding DMAHDM and NACP did not compromise the degree of conversion and contact angle of SB2 (p > 0.05). DMAHDM and NACP incorporation reduced the endogenous MMP activity by 53 %, facilitated remineralization, and increased the Young’s modulus of hybrid layer by 49 % after 3 months of aging in artificial saliva, compared to control. For SB2 Control, the dentin bond strength decreased by 38 %, with greater nanoleakage expression, after 3 months of aging (p < 0.05). However, DMAHDM+NACP group showed no loss in bond strength, with much less nanoleakage, after 3 months of aging (p > 0.05). SignificanceDMAHDM+NACP adhesive greatly reduced MMP-degradation activity in demineralized dentin, induced remineralization at adhesive-dentin interface, and maintained the dentin bond strength after aging, without adversely affecting polymerization and dentin wettability. This new adhesive has great potential to help eliminate secondary caries, prevent hybrid layer degradation, and increase the resin-dentin bond longevity.