PUBLICATION

Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance through Reverse Migration during Gouty Arthritis

Authors
Mohapatra, A., Rajendrakumar, S.K., Chandrasekaran, G., Revuri, V., Sathiyamoorthy, P., Lee, Y.K., Lee, J.H., Choi, S.Y., Park, I.K.
ID
ZDB-PUB-230117-11
Date
2023
Source
ACS applied materials & interfaces   15(3): 3812-3825 (Journal)
Registered Authors
Choi, Seok-Yong
Keywords
gout, macrophage polarization: Inflammation, nanoscavenger, neutrophil reverse migration
MeSH Terms
  • Animals
  • Arthritis, Gouty*/chemically induced
  • Arthritis, Gouty*/drug therapy
  • Cyclooxygenase 2
  • Cytokines
  • Disease Models, Animal
  • Inflammation/chemically induced
  • Inflammation/drug therapy
  • Macrophages
  • Mice
  • Neutrophils
  • Reactive Oxygen Species/adverse effects
  • Uric Acid
  • Zebrafish
PubMed
36646643 Full text @ ACS Appl. Mater. Interfaces
Abstract
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.
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