H ₂ S‐Amplified “Three‐in‐One” Antibacterial Strategy for Periodontitis Treatment Using a Photosensitive Pillararene‐Embedded COF/MOF Hybrid

ABSTRACT Reactive oxygen species (ROS)‐based nanomedicine holds great promise for combating biofilm‐associated infections (BAIs). Nonetheless, the strong antioxidant systems in these microenvironments lessen the effectiveness of ROS. The combination of ROS generation and depletion of antioxidant pathways is a potential approach to this issue. Herein, we present COF/HKUST‐10, a composite platform of a copper‐based metal‐organic framework (HKUST‐1) and pillararene‐embedded covalent organic frameworks for BAIs. Both endogenous hydrogen sulfide and exogenous light activate this platform, thereby inducing synergistic catalytic reactions that enhance ROS generation and local antioxidant inhibition. Transcriptomic analysis revealed that ROS and Cu ⁺ /Cu ²⁺ overload disrupted porphyrin metabolism in Porphyromonas gingivalis , severely impairing its energy metabolism and pathogenicity. This synergistic “three‐in‐one” antibacterial strategy involves ROS amplification, antioxidant system depletion, and copper ion‐mediated bactericidal effects. The experiments demonstrated the material's exceptional efficacy, resulting in robust antibacterial activity, efficient biofilm eradication, and significant reduction in inflammation. This study presents a distinctive strategy to enable synergistic treatment of BAIs, broadening the practical applications of supramolecular materials in biomedical applications.