Precise Strain Tuning of PtPdRhNi Nanozyme Boosts Multi‐Pathogen and Multi‐Model Antibacterial Therapy

Nanozymes are emerging antimicrobial agents that catalyze reactive oxygen species to eliminate pathogenic threats; however, their ability to combat multidrug-resistant infections remains limited by catalytic efficiency, substrate affinity and instability. Herein, we report a new strategy incorporating Ni into ultrathin PtPdRh nanosheets to engineer lattice strain for enhancing substrate affinity and boosting enzyme-mimicking catalytic activity. The PtPdRhNi nanozyme achieves a catalytic efficiency (K_cat/K_m = 2.05 × 10⁶ m^-1 s^-1), 56.5-fold higher than PtPdRh and maintains over 90% activity after 15 months. Theoretical calculations reveal Ni incorporation upshifts the d-band center from -1.80 to -1.27 eV and strengthens Pt─O bonding, thus accelerating the activation of H₂O₂ into ·OH. We further demonstrate that PtPdRhNi co-treated with H₂O₂ achieves 100% eradication of methicillin-resistant Staphylococcus aureus and Escherichia coli, as well as over 99.97% killing of Streptococcus mutans and Porphyromonas gingivalis. Across rat periodontitis, MRSA-infected skin wounds and deep abscess models, this catalytic platform enables rapid bacterial clearance, resolves inflammation and regenerates collagen-rich tissue. Transcriptomic analysis of MRSA exposed to PtPdRhNi with H₂O₂ identifies 1048 differentially expressed genes, revealing respiratory chain and tricarboxylic acid cycle shutdown, weakened antioxidant defenses, leading to energy exhaustion, oxidative damage and transcriptomic reprogramming.