# Combined strategy of dual-module cerium nanosystem composite extracellular vesicles regulate ROS in the tissue microenvironment to promote periodontitis recovery

## TL;DR

A new nanosystem using cerium-based components helps fight periodontitis by killing bacteria and reducing inflammation to promote healing.

## Contribution

A dual-module cerium nanosystem with antibacterial and immunomodulatory functions is developed for periodontitis treatment.

## Key findings

- Ce-N-C@HA nanozymes generate hydroxyl radicals to target and eliminate pathogens in periodontal pockets.
- CeO2-EV nanocomposites scavenge ROS and induce M2 macrophage polarization, reducing inflammation.
- The combined strategy improves the periodontal microenvironment and promotes tissue regeneration.

## Abstract

Periodontal disease, a chronic inflammatory condition driven by dysbiotic biofilms and host immune dysregulation, lacks therapeutic strategies that simultaneously eliminate infection, resolve inflammation, and promote tissue regeneration. To bridge this gap, we designed a spatially compartmentalized dual-module nanosystem with ‘one cerium, dual functions’. Specifically, the antibacterial module utilizes hyaluronic acid (HA)-modified single-atom cerium nanozymes (Ce-N-C@HA) delivered to periodontal pockets. Upon HA degradation by bacterial hyaluronidase, the exposed catalytic sites generate hydroxyl radicals (·OH) via peroxidase like (POD-like) activity, enabling targeted pathogen eradication. Concurrently, the immunomodulatory module delivers Lactobacillus reuteri-derived extracellular vesicles (EVs) loaded with ultra-small CeO2 nanoparticles (CeO2-EV) into subgingival tissues. This module efficiently scavenges reactive oxygen species (ROS) and induces macrophage polarization to M2 anti-inflammatory phenotype, significantly alleviating the inflammatory microenvironment. By utilizing cerium’s dual functionalities which localized antibacterial action and reconstructs immune homeostasis, this system improves the periodontal microenvironment and promotes tissue regeneration, providing a novel strategy for nanotherapy in oral inflammatory diseases.

Image 1

•Two different structures of cerium nanozymes (Ce-N-C and CeO2) constructed innovatively results in different activities.•A novel Ce SAzyme (Ce-N-C) exhibits peroxidase-like activity, which is developed for antibacterial application.•The CeO2-EV nanocomposite scavenges ROS and modulates immunity, promoting macrophage polarization to M2 phenotype.•This “One cerium, dual functions” combined strategy provides a novel and efficient paradigm in periodontitis treatment.

Two different structures of cerium nanozymes (Ce-N-C and CeO2) constructed innovatively results in different activities.

A novel Ce SAzyme (Ce-N-C) exhibits peroxidase-like activity, which is developed for antibacterial application.

The CeO2-EV nanocomposite scavenges ROS and modulates immunity, promoting macrophage polarization to M2 phenotype.

This “One cerium, dual functions” combined strategy provides a novel and efficient paradigm in periodontitis treatment.