Cascade Nanozyme-Catalyzed Tophi Dissolution and ROS Scavenging for Anti-Inflammatory Therapy in Gouty Arthritis

Area of Science:

• Biomaterials Science
• Nanomedicine
• Rheumatology

Background:

• Tophi, caused by monosodium urate (MSU) crystal deposition, are challenging to treat due to limited drug efficacy and risks associated with surgical removal.
• Intraoperative MSU release during surgery can induce severe oxidative stress and inflammation.
• Current treatments for tophi often lack efficacy or carry significant risks.

Purpose of the Study:

• To develop a novel nanozyme, Ce-MOF@Pt, for synergistic clearance of MSU crystals and scavenging of reactive oxygen species (ROS).
• To evaluate the efficacy of Ce-MOF@Pt in treating MSU-induced gouty arthritis with a focus on minimally invasive tophi dissolution and inflammation reduction.

Main Methods:

• Development of a cascade nanozyme, Ce-MOF@Pt, integrating platinum (Pt) nanoparticles within a cerium-based metal-organic framework (Ce-MOF).
• In vitro assessment of Ce-MOF@Pt's ability to dissolve MSU crystals, scavenge ROS, and modulate macrophage activity.
• In vivo evaluation in a mouse model of MSU-induced gouty arthritis, assessing pain, joint inflammation, and molecular mechanisms via transcriptomics.

Main Results:

• Ce-MOF@Pt demonstrated oxidase-like activity to dissolve MSU crystals and produce allantoin, while the Ce-MOF matrix provided catalase and superoxide dismutase-like activities for ROS scavenging.
• The nanozyme exhibited pH-responsive activity switching, enhancing its therapeutic efficiency.
• In vitro studies showed reduced inflammation via ROS scavenging and macrophage reprogramming. In vivo, Ce-MOF@Pt alleviated pain and joint inflammation in mice, mitigating endoplasmic reticulum stress.

Conclusions:

• The Ce-MOF@Pt nanozyme offers a promising, minimally invasive therapeutic strategy for tophi dissolution.
• This approach effectively prevents MSU-induced inflammation by addressing both crystal deposition and oxidative stress.
• Ce-MOF@Pt presents a novel solution for managing gouty arthritis by providing integrated anti-oxidative therapy.