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PH-Responsive PtPdRuRhIr High-Entropy Alloy Nanozymes with Switchable Catalysis for Exceptional Inflammation Inhibition and Oral Bone Protection

ABSTRACT: The treatment of periodontal disease, driven by resilient bacterial biofilms and oxidative stress, remains a significant clinical challenge. Current therapies struggle to effectively eliminate resistant biofilms and resolve inflammation simultaneously. Here, we report the de novo design of high-entropy alloy (HEA, PtPdRuRhIr)-based Janus artificial enzymes with pH-gated redox biocatalysis for periodontitis therapy. The multi-metal synergy stabilizes the d-band center, enabling pH-dependent transitions between peroxidase-like activities in acidic conditions and antioxidase-like functions at neutral pH. At the infection stage, the Janus artificial enzymes generate bactericidal reactive oxygen species (ROS), eliminating Staphylococcus aureus (S. aureus) and Porphyromonas gingivalis (P. gingivalis). While during the healing process, they scavenge excess ROS to alleviate oxidative stress and promote tissue regeneration. In vitro and in vivo studies confirm their ability to disrupt biofilms, reduce inflammation, and support alveolar bone regeneration. By integrating antimicrobial activity with immunomodulation in a single nanoplatform, this pH-responsive nanozyme offers a promising strategy for the treatment of periodontitis and other biofilm-associated inflammatory diseases, advancing both infection control and tissue repair.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE307291 | GEO | 2026/09/09

REPOSITORIES: GEO

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Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.

Project description:Background The Gram-negative bacteria Fusobacterium nucleatum and Porphyromonas gingivalis are associated with periodontitis and members of a complex microbial biofilm. The self-produced extracellular polymeric matrix (EPM) of biofilms generally consists of lipids, exopolysaccharides, nucleic acids and proteins. The proteinaceous components of the biofilm matrix play many roles in biofilm development and function. In this study the protein composition of the matrices in mono- and dual-species biofilms of F. nucleatum and P. gingivalis were analyzed. Methods The bacteria were grown in a static biofilm model. Extraction of EPM was performed by careful mechanical shearing and filtration. Initial tryptic digestion of EPMs was followed by liquid chromatography-tandem mass spectrometry to analyze the resulting peptide mixtures. Quantitative proteomic software MaxQuant was then employed for protein identifications and label-free quantitative (LFQ) analysis. Functional analyses of identified proteins were applied in classification and prediction of their possible roles in EPM. Results We identified 542 proteins in the matrix of F. nucleatum, 93 proteins in the matrix of P. gingivalis and 280 proteins in the dual-species biofilm matrix. Similarly, relative quantification based on LFQ intensity scores identified generally higher protein amounts in F. nucleatum and dual species EMPs, when compared to P. gingivalis EPM. Acetyl-CoA acetyltransferase, alkyl hydroperoxide reductase C22 protein, neutrophil-activating protein A, tryptophanase and glutamate dehydrogenase were the top five proteins in the matrix of F. nucleatum biofilm. The oxidoreductase NAD-specific glutamate dehydrogenase and the proteolytic and adhesive protein Lys-gingipain were most abundant in P. gingivalis EPM. In the dual species EPM, F. nucleatum contributed to four out of the five with glutamate dehydrogenase on top. NAD-specific dehydrogenase from P. gingivalis was among the top five. Functional analyses with respect to virulence for example, revealed the stress-induced protein yicC in F. nucleatum EPM, while hemagglutinin HagA and fimbriae minor component FimD were among the top 5 in P. gingivalis EPM. Conclusions We showed that the biofilm matrix of two important periodontal pathogens is abundant in proteins and nearly 70% of all EPM proteins originate from F. nucleatum when grown together with P. gingivalis. Outer membrane proteins, virulence related and oxidative stress proteins were among the most abundant proteins identified.

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PH-Responsive PtPdRuRhIr High-Entropy Alloy Nanozymes with Switchable Catalysis for Exceptional Inflammation Inhibition and Oral Bone Protection

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