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화순전남대학교병원

Chem. Eng. J., Available online 22 May 2025, 164064 | https://doi.org/10.1016/j.cej.2025.164064 A Dual-Modality nanozyme Exploiting ROS-Responsive oxygen Catalysis for Precision NF-κB pathway Suppression in gouty arthritis

Sathiyamoorthy Padmanaban^a,1, Sree Samanvitha Kuppa^a,b,c,1, Omkar Sangabathula^d, Amal Babu ^a, Adityanarayan Mohapatra^a,e, Sung Sun Kim ^f, Hong Yeol Yang ^b,c, Aravindkumar Sundaram^a,e, Hyung Keun Kim ^b,c, Jong Keun Seon ^a,b,c, In-Kyu Park ^a,e

^aDepartment of Biomedical Sciences and BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School, Hwasun 58128, Republic of Korea
^bDepartment of Orthopaedics Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Jeonnam 519-763, Republic of Korea
^cKorea Biomedical Materials and Devices Innovation Research Center of Chonnam National University Hospital, 42, Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea
^dDepartment of Chemical Engineering, Indian Institute of Technology, Hyderabad Kandi 502284 Telangana, India
^eDRCure Inc. Hwasun 58128, Republic of Korea
^fDepartment of Pathology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea

¹Equal contributions.
Corresponding authors : Hyung Keun Kim, Jong Keun Seon, In-Kyu Park

Abstract

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.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-29)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오소재

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