Spatiotemporally Responsive BEC Nanoplatform Targets Neutrophils to Reprogram Immune Crosstalk and Alleviate Periodontal Inflamm‐Ageing in Periodontitis

AIM: To investigate the underlying mechanism of immune cell crosstalk in periodontal inflammatory ageing and to explore potential pharmaceutical interventions for safely reversing this process. MATERIALS AND METHODS: Bovine serum albumin-epigallocatechin gallate-copper nanoparticles (BEC NPs) were synthesised by coating a bovine serum albumin membrane onto an epigallocatechin gallate-copper-phenolic network. BEC NPs' regulatory impacts on the fate of neutrophils and macrophages were evaluated through immunofluorescence staining, PCR, RNA sequencing and Western blot analysis. Their anti-senescence effects on gingival fibroblasts were assessed using cell migration assays and SA-β-gal staining, while an experimental periodontitis rat model was established to validate the in vitro findings. RESULTS: Accumulating evidence indicated that pH-responsive nanoparticles alleviated periodontal inflamm-ageing through modulation of neutrophil-macrophage crosstalk. Functional analyses revealed that BEC NPs suppressed neutrophil extracellular trap formation via dual mechanisms: reactive oxygen species scavenging to sustain mitochondrial integrity, and actin cytoskeleton stabilisation to inhibit nuclear translocation of neutrophil elastase and myeloperoxidase. In vivo assessment demonstrated that BEC NPs exhibited a favourable biosafety profile and significant therapeutic efficacy in suppressing the progression of periodontal inflammation. CONCLUSION: This study presents a smart nanosystem-based 'endogenous homeostasis reconstruction' strategy, offering programmable, early-stage intervention for periodontal inflamm-ageing with considerable clinical translation prospects.