Presentation Information
[P04-502]A Dual-Modality nanozyme Exploiting ROS-Responsive oxygen Catalysis for Precision NF-κB pathway Suppression in gouty arthritis
○In-Kyu Park1, Soo-Hong Lee2 (1. Chonnam National University (Korea), 2. Dongguk University (Korea))
Keywords:
Gout,Inflammation,Cerium oxide,Drug release,Alpha lipoic acid
Gout is characterized by urate deposition in joints leading to immune cell recruitment and inflammatory cytokine release. This condition poses significant therapeutic challenges due to its association with the activation of the nuclear factor (NF)-κB pathway, which promotes inflammation. Traditional treatment modalities often fall short of effectively targeting gout pathophysiology. To address this gap, nanoparticles present a promising avenue by improving drug bioavailability and reducing toxicity. This study explores the therapeutic potential of hollow cerium oxide (CeO) nanoparticles loaded with alpha-lipoic acid (α-LA) in alleviating NF-κB pathway activation. Synthesized through the solvothermal method, hollow CeO nanoparticles were loaded with α-LA through solvent evaporation. Characterization revealed a hollow spherical morphology, uniform size distribution, and sustained α-LA release in vitro. Treatment with CeO nanoparticles, α-LA, and CeO-loaded α-LA resulted in decreased levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), and nitric oxide (NO), alongside increased antioxidant enzyme activities (superoxide dismutase and catalase). Moreover, the nanoparticle efficacy was evaluated in RAW 264.7 macrophage cells stimulated with monosodium urate (MSU) and in a murine model of MSU-induced joint inflammation. While CeO nanoparticles and α-LA individually exhibited moderate reductions in inflammatory mediator release and NF-κB pathway activity, CeO-loaded α-LA synergistically suppressed MSU-induced NF-κB pathway activation. Notably, CeO-loaded α-LA also ameliorated MSU-induced joint inflammation in mice. These findings explore the therapeutic potential of α-LA-loaded CeO nanoparticles, a novel formulation combining antioxidant and anti-inflammatory nanocarriers, to mitigate MSU-induced NF-κB activation. The hollow spherical nanoparticles enable controlled α-LA release, enhancing bioavailability and targeting dual pathways of oxidative stress and inflammation—a strategy not yet reported in gout management.
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