Structure-Tailoring Cerium Nanozymes with Self-Cascade ROS Scavenging Catalysis Modulate the Microbiota-Gut-Joint...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Microbiology

Background:

• Rheumatoid arthritis (RA) is linked to gut microbiota dysbiosis and inflammation driven by reactive oxygen species (ROS).
• Existing treatments often neglect the cascade of ROS generation and its impact on the gut-joint axis.
• Targeting the gut microbiota presents a promising therapeutic avenue for RA.

Purpose of the Study:

• To develop a valence-engineered nanozyme with self-cascade catalytic activity for continuous ROS scavenging.
• To investigate the nanozyme's ability to restore gut microbiota homeostasis and attenuate joint inflammation in rheumatoid arthritis.
• To establish a design paradigm for gut microenvironment-adapted nanozymes for early RA intervention.

Main Methods:

• Fabrication of a cerium oxide (CeO_X)-based nanozyme with tunable Ce³⁺/Ce⁴⁺ ratios via gold (Au) deposition.
• Encapsulation of the nanozyme with sodium alginate (SA) for oral administration and gastric acid resistance.
• Evaluation of the nanozyme's ROS scavenging efficiency, oxygen generation suppression, gut microbiota restoration, and anti-inflammatory effects in a rat model of rheumatoid arthritis.

Main Results:

• The Au-deposited CeO_X nanozyme exhibited enhanced oxygen vacancy generation and efficient ROS scavenging via a superoxide anion→hydrogen peroxide→hydroxide ion conversion pathway.
• Oral administration of Au/CeO_X(0.93)@SA restored gut microbial balance and normalized short-chain fatty acid profiles in RA model rats.
• Significant attenuation of joint inflammation, cartilage degradation, and reduction in systemic pro-inflammatory cytokines were observed, alongside improved intestinal barrier integrity.

Conclusions:

• The developed nanozyme effectively scavenges ROS and restores gut microbiota homeostasis, offering a dual-action therapeutic strategy for rheumatoid arthritis.
• This study presents a novel design paradigm for gut microenvironment-adapted nanozymes for early intervention in RA.
• The findings highlight the potential of targeting the microbiota-gut-joint axis through advanced nanozyme engineering.