Adityanarayan Mohapatra ¹, Santhosh Kalash Rajendrakumar ^{1 2}, Gopalakrishnan Chandrasekaran ¹, Vishnu Revuri ³, Padmanaban Sathiyamoorthy ¹, Yong-Kyu Lee ³, Jae Hyuk Lee ⁴, Seok-Yong Choi ¹, In-Kyu Park ¹

¹Department of Biomedical Sciences and Center for Global Future Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
²Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom.
³Department of Green Bioengineering, Korea National University of Transportation, Chungju 27470, Republic of Korea.
⁴Department of Pathology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.

Corresponding Author : In-Kyu Park 

The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty arthritis. Herein, a peroxidase-mimicking nanoscavenger was developed by forming manganese dioxide over albumin nanoparticles loaded with an anti-inflammatory drug, indomethacin (BIM), to block the secretion of ROS and COX2-induced proinflammatory cytokines in the MSU-induced gouty arthritis model. In the MSU-induced arthritis mouse model, the BIM nanoparticles alleviated joint swelling, which is attributed to the abrogation of ROS and inflammatory cytokine secretions from proinflammatory macrophages that induces neutrophil infiltration and fluid building up in the inflammation site. Further, the BIM nanoparticle treatment reduced the influx of macrophages and neutrophils in the injured region by blocking migration and inducing reverse migration in the zebrafish larva tail amputation model as well as in MSU-induced peritonitis and air pouch mouse models. Overall, the current strategy of employing biomineralized nanoscavengers for arthritis demonstrates clinical significance in dual blocking of peroxides and COX2 to prevent influx of inflammatory cells into the sites of inflammation.