Spatiotemporally Responsive BEC Nanoplatform Targets Neutrophils to Reprogram Immune Crosstalk and Alleviate...

To investigate the underlying mechanism of immune cell crosstalk in periodontal inflammatory ageing and to explore potential pharmaceutical interventions for safely reversing this process.

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.

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.

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.