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Nanomachines are a new type of antibacterial agent that can eliminate pathogenic threats by catalyzing reactive oxygen species (ROS); however, their ability to combat multi-drug resistant (MDR) infections is still limited by catalytic efficiency, substrate affinity, and instability. In this study, the team reported a new strategy of incorporating Ni into ultrathin PtPdRh nanosheets to construct lattice strain, aiming to enhance substrate affinity and improve the enzyme-like catalytic activity. The PtPdRhNi nanomachine achieved a catalytic efficiency of 2.05 x 10⁷ M⁻¹ s⁻¹ (Kcat/Km), which was 56.5 times higher than PtPdRh, and maintained over 90% activity after 15 months. Theoretical calculations indicated that the incorporation of Ni shifted the d-band center from -1.80 eV to -1.27 eV and strengthened Pt-O bonding, thereby accelerating the activation of H₂O₂ to ·OH. The team further demonstrated that the synergistic treatment of PtPdRhNi with H₂O₂ could achieve 100% eradication of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli, as well as over 99.97% killing of Streptococcus mutans and Porphyromonas gingivalis. In rat periodontal inflammation, MRSA-infected skin wounds, and deep abscess models, this catalytic platform could achieve rapid bacterial clearance, alleviate inflammation, and regenerate collagen-rich tissues. Transcriptomic analysis of MRSA treated with PtPdRhNi and H₂O₂ identified 1048 differentially expressed genes, revealing the closure of the respiratory chain and the tricarboxylic acid (TCA) cycle, and the weakening of antioxidant defense, which led to energy depletion, oxidative damage, and transcriptional reprogramming. This study was published in "Advanced Materials" under the title "Precise Strain Tuning of PtPdRhNi Nanozyme Boosts Multi-Pathogen and Multi-Model Antibacterial Therapy".
Research background: Bacterial infections, especially those caused by multi-drug resistant pathogens, remain a pressing global health challenge, causing over 700,000 deaths each year and projected to cause 10 million deaths annually by 2050 [1-3]. The excessive and inappropriate use of antibiotics has accelerated the emergence of "super bacteria", and the discovery of new antibiotics since the 1980s has stagnated, highlighting the urgent need for alternative antibacterial strategies that bypass traditional antibiotic resistance pathways [4-7]. Nanomachines, especially those based on precious metals, have attracted attention in antibacterial therapy due to their strong enzyme-like catalytic activity (such as peroxidase, catalase, superoxide dismutase, and oxidase), significant structural stability, and adaptability to complex physiological environments [8-11]. To combat bacterial infections, nanomachines catalyze the production of reactive oxygen species, triggering oxidative stress, disrupting cell membranes, and causing bacterial death, while having low risk of resistance and good biocompatibility [12-14]. However, the antibacterial efficacy of precious metal nanomachines against high-pathogenicity and multi-drug resistant bacteria is still far from satisfactory. A key limitation lies in their inherent inert electronic structure, where the d-band center deviates from the optimal adsorption position, resulting in weak substrate affinity and slow catalytic rate at low H₂O₂ concentrations. Additionally, the mismatch between the strength of metal-oxygen bonds and the preferred reaction pathway limits the formation and conversion of reaction intermediates. Strategies such as adjusting particle size, crystallinity, alloy composition, or ligand environment can improve the enzyme reaction performance to a certain extent [15-17]; However, these methods have limited control over the electronic state of the active site, and are insufficient to overcome the inherent lattice rigidity of precious metals. This inherent lattice rigidity hinders the fine-tuning of the d-band center and metal-oxygen bonding, thereby restricting the thermodynamic and kinetic regulation of H2O2 adsorption and activation. Developing strategies to precisely control the inherent lattice rigidity of precious metal nanoenzymes at the atomic scale to overcome their insufficient H2O2 adsorption and activation in enzymatic reactions is crucial for achieving efficient antibacterial treatment, but this remains a formidable challenge.
Research Overview: The team reported a Ni-doping strategy that induces atomic-scale lattice strain in ultrathin PtPdRh nanosheets, generating a local stress field, thereby reshaping the electronic structure of the active site and raising the d-band center, thereby enhancing H2O2 adsorption, reaction kinetics, and peroxidase (POD)-like activity. Enzyme kinetics analysis showed that the H2O2 binding affinity (Km = 0.07 mM) of PtPdRhNi nanoenzymes was 24.1 times higher than that of PtPdRh, and the catalytic efficiency (Kcat/Km = 2.05 x 10⁷ M⁻¹ s⁻¹) was 56.5 times higher, while maintaining over 90% activity after 15 months. Density functional theory (DFT) analysis and experimental identification of key oxidation intermediates confirmed that Ni doping disrupted the local coordination geometry and triggered significant lattice strain, which redistributed the electronic state, raised the d-band center, and strengthened the Pt-O interaction, thereby lowering the energy barrier for the gradual activation of H2O2 to form ·OH. When combined with H2O2, the PtPdRhNi nanoenzyme eliminated methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), and also eliminated over 99.97% of Streptococcus mutans and Porphyromonas gingivalis. This unprecedented antibacterial efficacy was consistently demonstrated in three challenging infection models (rat periodontitis, MRSA-infected skin wounds, and deep abscesses), achieving rapid bacterial clearance, significant inflammation relief, and collagen-rich tissue regeneration. Comprehensive transcriptomic analysis of MRSA treated with PtPdRhNi + H2O2 revealed 1048 differentially expressed genes, reflecting a systemic stress response, including strong induction of heat shock and nucleic acid repair programs, as well as significant inhibition of tricarboxylic acid (TCA) cycle activity, respiratory chain function, amino acid biosynthesis, and nitrogen metabolism. This coordinated closure of energy and nutrient metabolism, combined with the damaged redox enzyme system, led to energy depletion and oxidative damage, ultimately resulting in bacterial death.
Paper Link (DOI): https://doi.org/10.1002/adma.202518526
