Chloroplast-mimicking nanocapsules for sequential therapy of white spot

Effective management of white spot lesions requires simultaneous recovery of function and aesthetics. Current caries remineralization therapy (CRT) can restore enamel hardness but remains inadequate in achieving complete visual normalization of these lesions. Such an obstacle mainly arises from remaining cariogenic biofilms that maintain an acidic, poorly permeable microenvironment, thereby limiting remineralizing-ion diffusion while disturbing organized formation of enamel crystals and ultimately compromising visual outcomes. Although various CRT strategies have been combined with antimicrobial approaches, biofilm remnants frequently remain when remineralization is initiated, continuing to impair treatment efficacy. Here, we propose the concept of sequential therapy of white spot lesions, inspired by chloroplast architecture, to achieve staged biofilm clearance and remineralization. We developed phase-change nanocapsules integrating dextranase and mutanase for extracellular matrix (ECM) degradation, lysozyme for bacterial elimination, and tannic acid-modified black phosphorus for photothermal activation and phosphate release. Upon light triggering via photothermal conversion, the nanocapsules first degrade ECM to disrupt biofilm structure and physically expose bacteria, thereby enhancing lysozyme-mediated killing, and then help establish a clean lesion surface while initiating and sustaining enamel remineralization. In vitro, enamel hardness was substantially restored within 9 days, and white spot lesions showed improved visual appearance. This integrated nanoplatform demonstrates a proof-of-concept sequential anti-biofilm and remineralization strategy for functional restoration with partial aesthetic improvement in white spot lesion therapy.