Light-Activated Ruthenium Nanoclusters Reprogram the Metabolic-Quorum Sensing Axis for Precision Periodontitis...

Periodontitis is a polymicrobial disease driven by metabolic interdependencies, wherein commensal bacteria fuel the virulence of keystone pathogens like Porphyromonas gingivalis (P. gingivalis). In particular, Veillonella parvula (V. parvula) supplies essential nutrients to the keystone pathogen P. gingivalis, enabling its virulence even at low abundance. Therefore, targeting V. parvula nitrate metabolism to deprive P. gingivalis of nutrients and attenuate its virulence represents a promising therapeutic strategy for controlling periodontitis progression. We engineered L-cysteine-capped ruthenium nanoclusters (Ru NCs) that efficiently reduce nitrate to ammonium under 660 nm light. This photocatalytic conversion depleted the bioavailable nitrate pool associated with V. parvula metabolism, disrupting amino acid production and quorum-sensing-related support for P. gingivalis. Consequently, Ru NCs potently reduced biofilm biomass and thickness, suppressed P. gingivalis activity, and downregulated its key virulence genes (RgpA/B, Kgp, FimA). Multiomics analyses supported nitrate-dependent metabolic collapse in V. parvula, which was associated with downstream energy and biosynthetic impairment in P. gingivalis. In a rat periodontitis model, light-activated Ru NCs attenuated alveolar bone loss, preserved collagen, and shifted the local cytokine profile from pro-inflammatory (IL-6) to anti-inflammatory (Arg-1). This work provides a proof-of-concept strategy for targeting defined interspecies metabolic interactions, offering a new paradigm for microbiome-targeted therapy.