ObjectiveThis study investigated the effects of mineralizing film consisting of hydroxypropyl methylcellulose (HPMC) and amorphous fluorinated calcium phosphate (AFCP) nanoparticles on enamel white spot lesions (WSLs).Material and MethodsThe AFCP nanoparticles and mineralizing film were prepared via nanoprecipitation and solvent evaporation, respectively. They were characterized with Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectrometry (ICP-AES), and fluoride ion selective electrode. Thirty-two human enamel slices (4 mm × 4 mm × 1.5 mm) were highly polished and randomly assigned to four groups: negative control (no treatment); pure HPMC film; mineralizing film; GC Tooth Mousse Plus® (contains 10% CPP-ACP and 0.2% NaF). Subsequently, samples were challenged by a modified pH-cycling and characterized by color measurement, Micro-CT, SEM/EDX, and nanoindentation.ResultsThe mineralizing film could sustain release of Ca, P and F ions over 24 h and maintain AFCP nanoparticles in metastable state over 8~12 h. During 4 weeks of pH cycling, the mineralizing film group exhibited least color change (∆E), mineral loss and lesion depth (120 ± 10 µm) among four groups (p < 0.05). SEM findings revealed that the porosities among enamel crystals increased in negative control and pure HPMC film groups after pH cycling, whereas in mineralizing film group, the original microstructure of enamel was well conserved and mineral deposits were detected between enamel prisms. Mineralizing film group demonstrated a least reduction of nanomechanical properties such as elastic modulus of 77.02 ± 6.84 GPa and hardness of 3.62 ± 0.57 GPa (p < 0.05).ConclusionThe mineralizing film might be a promising strategy for prevention and management of WSLs via inhibiting enamel demineralization and promoting enamel remineralization.