Demineralized collagen fibers at the hybrid layer are susceptible of degradation.Remineralization may aid to improve bond longevity. Objectives: to infiltrate zinc and calcium-loaded polymeric nanoparticles into demineralized dentin to facilitate hybrid layer remineralization. Materials and Methods: Zinc or calcium-loaded polymeric nanoparticles were infiltrated into etched dentin and Single Bond adhesive was applied.Bond strength was tested after 24 hours and six months storage. Nanomechanical properties, dye-assisted confocal laser microscopy and Masson's trichrome staining evaluation were performed to assess for the hybrid layer morphology, permeability and remineralization ability after 24 hours and three months. Data were analyzed by ANOVA and Student-Newman-Keuls multiple comparisons tests (p<0.05). Results:Immediate bond strength was not affected by nanoparticles infiltration (25 to 30 MPa), while after 6 months bond strengths were maintained (22 to 24 MPa). After 3 months, permeability occurred only in specimens in which nanoparticles were not infiltrated.Dentin remineralization, at the bottom of the hybrid layer, was observed in all groups.After microscopy analysis, zinc-loaded nanoparticles were shown to facilitate calcium deposition throughout the entire hybrid layer. Young's modulus at the hybrid layer increased from 2.09 to 3.25 GPa after 3 months, in specimens with zinc nanoparticles; meanwhile, these values were reduced from 1.66 to 0.49 GPa, in the control group.Conclusions: Infiltration of polymeric nanoparticles into demineralized dentin increased long-term bond strengths. Zinc-loaded nanoparticles facilitate dentin remineralization within the complete resin-dentin interface. Clinical Relevance: Resin-dentin bond longevity and dentin remineralization at the hybrid layer were facilitated by zinc-loaded nanoparticles.