Objectives: To achieve in vitro remineralization of enamel white spot lesions (WSLs) via a mesoporous delivery system of amorphous calcium phosphate (ACP) precursors.Materials and methods:Amine-functionalized expanded pore mesoporous silica (aMSN) was loaded with polyacrylic acid-stabilized amorphous calcium phosphate (PAA-ACP) to develop a carrier-based delivery system (PAA-ACP@aMSN). Thirty-six artificial WSLs samples were created and randomly assigned to three treatments: artificial saliva solution (negative control, n = 12), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) slurry (n = 12), and PAA-ACP@aMSN slurry (n = 12). Surface microhardness, Raman intensity, and color were measured before/after artificial demineralization and after remineralization treatments to evaluate the remineralization level of each sample. SEM images were taken on the surface and cross-section of samples to observe microstructure changes.Results:The surface microhardness recovery ratio (%SMHRR), Raman intensity change ratio (%ICR), and color recovery ratio (%CRR) were not significantly different between CPP-ACP and PAA-ACP@aMSN groups (P > 0.05), but both of them had significantly higher %SMHRR, %ICR, and %CRR values than negative control (P < 0.01). SEM images showed that apparent enamel prism imprints and inter-prism gaps in negative control were masked by mineral deposition in the PAA-ACP@aMSN and CPP-ACP groups.Conclusions: PAA-ACP@aMSN has an ability to remineralize enamel WSLs.Clinical relevance: The carrier-based amorphous calcium phosphate delivery system has great potential to serve as a remineralizing agent for the treatment of WSLs.