High-Entropy Alloy-Based Artificial Enzymes With Modulated D-Band Center and pH-Controllable ROS Biocatalysis for Stage-Specific Treatment of Inflammatory and Infectious Oral Diseases

Abstract

Periodontitis, characterized by tenacious polymicrobial biofilms and persistent oxidative stress, presents a formidable therapeutic challenge in clinical practice. Current treatment modalities often fall short in achieving simultaneous biofilm eradication and inflammatory resolution. Here, we present the de novo design of high-entropy alloy (HEA, PtPdRuRhIr)-based artificial enzymes with modulated d-band center and pH-controllable biocatalysis of reactive oxygen species (ROS) for stage-specific treatment of inflammatory and infectious periodontitis. Our studies demonstrate that the unique structure of PtPdRuRhIr-based HEA stabilizes the d-band center, enhances the electron density of Ru atoms, and optimizes the binding strength of oxygen species, thus enabling exceptional ROS biocatalysis and pH-controllable switching between antioxidase-like functions at physiological pH conditions and peroxidase-like activity under acidic infectious environments. Therefore, the PtPdRuRhIr-based HEA simultaneously exhibits superior regenerative functions by mitigating oxidative damage and bioadaptive antibacterial properties by generating bactericidal ROS. Comprehensive in vitro and in vivo evaluations demonstrate suppression of inflammatory cytokines, functional regeneration of alveolar bone, and also microenvironment-adaptive disruption of biofilm. By integrating pH-dependent anti-inflammatory and antimicrobial activities with immunomodulatory capacity in a single nanoplatform, this smart biocatalyst represents a promising therapeutic strategy for periodontitis and other biofilm-associated inflammatory disorders, effectively bridging the gap between microbial clearance and tissue restoration.