Constructing Dual-Atomic FeFe Sites Nanozyme for Targeted Osteoarthritis Therapy through Mitigating Oxidative Stress

Ting Ying1, Qi Wang2, Dejian Li2

  • 1Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, 200092, China.

Insights

This study introduces novel nanozymes (Fe2-NCs) that neutralize harmful reactive oxygen species (ROS) to protect cartilage and chondrocytes, offering a new therapeutic strategy for osteoarthritis.

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Biochemistry

Background:

  • Osteoarthritis (OA) progression is exacerbated by excessive reactive oxygen species (ROS), leading to chondrocyte and articular cartilage damage.
  • Current treatments often fail to address the underlying oxidative stress driving OA pathogenesis.

Purpose of the Study:

  • To develop novel dual-site nanozymes, Fe─Fe dimers on nitrogen-doped porous carbon (Fe2-NCs), for effective ROS scavenging.
  • To investigate the therapeutic potential of Fe2-NCs in mitigating oxidative stress and protecting against OA progression.

Main Methods:

  • Synthesis of Fe2-NCs with dual-site nanozyme activity.
  • Utilizing co-adsorption mechanisms for superoxide radical elimination.
  • Employing Density Functional Theory (DFT) for mechanistic insights.
  • Conducting in vitro and in vivo experiments to assess efficacy.

Main Results:

  • Fe2-NCs demonstrated enhanced ROS scavenging, mimicking antioxidant enzymes.
  • DFT calculations revealed synergistic Fe─Fe dimer effects accelerating O─O bond cleavage.
  • Fe2-NCs protected chondrocytes from apoptosis, improved mitochondrial function, and normalized key protein expressions (NOX4, ATP, COXIV).
  • Fe2-NCs inhibited pro-inflammatory mediators (COX-2), cartilage-degrading enzymes (MMP-13), and collagen breakdown via the NF-κB pathway.

Conclusions:

  • Fe2-NCs represent a promising nanozyme strategy for OA treatment by effectively combating oxidative stress.
  • The developed nanozymes offer multi-faceted protection against OA pathogenesis, including chondrocyte survival and cartilage preservation.