Nanozymes for periodontal biofilm-associated challenges: mechanisms, platforms, and translational perspectives

Periodontitis is a chronic inflammatory disease driven by dysbiotic subgingival biofilms whose extracellular polymeric substance (EPS) matrix confers marked resistance to conventional therapies and host immunity, with antibiotic resistance further compounding the challenge. Nanozymes, as nanomaterials with intrinsic enzyme-like catalytic activities, offer a promising alternative due to their catalytic efficiency, stability, and multifunctionality. This narrative review synthesizes current evidence on nanozyme applications for overcoming biofilm-associated challenges in periodontitis, focusing on antibiofilm mechanisms, representative platforms, delivery strategies, and translational hurdles. A literature search was conducted across PubMed, Web of Science, and Scopus using keywords including "nanozyme," "periodontitis," and "biofilm." Nanozymes combat periodontal biofilms through complementary mechanisms: reactive oxygen species (ROS) generation via peroxidase- and oxidase-like activities to kill biofilm-embedded bacteria; degradation of EPS components including polysaccharides, proteins, and extracellular DNA; disruption of bacterial adhesion and quorum sensing; and modulation of inflammation via ROS scavenging through catalase- and superoxide dismutase-like activities. Representative platforms have been evaluated in diverse preclinical models including marginal periodontitis, apical periodontitis, and other biofilm-associated infections each with distinct levels of direct periodontal relevance. While some platforms have been validated directly in periodontitis models, others provide indirect evidence or mechanistic insights that inform translational potential. These include Ru-C3N4 single-atom nanozymes (tested in otitis media models), AgAu-CeO2 heterojunction nanozymes with probiotics, ferumoxytol (tested in apical periodontitis), mitochondria-targeted ferritin nanozymes, and Ru@COF nanozymes. Despite encouraging preclinical evidence, challenges in long-term biosafety, metal-ion accumulation, and clinical translation persist. Future research should prioritize standardized safety evaluation, biodegradable designs, and clinical validation to translate nanozyme-based therapies from bench to bedside.