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Published on: October 20, 2013
Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance
Adityanarayan Mohapatra1, Santhosh Kalash Rajendrakumar1,2, Gopalakrishnan Chandrasekaran1
1Department of Biomedical Sciences and Center for Global Future Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju61469, Republic of Korea.
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.
Insights
New nanoscavengers loaded with indomethacin effectively treat gouty arthritis by blocking reactive oxygen species (ROS) and inflammation, reducing joint swelling and immune cell infiltration.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunology
Background:
- Monosodium urate (MSU) crystal deposition in gouty arthritis triggers reactive oxygen species (ROS) and cytokine release from macrophages.
- This inflammatory cascade promotes leukocyte infiltration into joints, exacerbating arthritis symptoms.
Purpose of the Study:
- To develop a novel nanoscavenger system for treating MSU-induced gouty arthritis.
- To investigate the dual-blocking efficacy of nanoscavengers against ROS and cyclooxygenase-2 (COX2) pathways.
Main Methods:
- Albumin nanoparticles were loaded with indomethacin and coated with manganese dioxide to create BIM nanoscavengers.
- The efficacy of BIM nanoparticles was evaluated in mouse models of MSU-induced arthritis, peritonitis, and air pouch inflammation.
- Zebrafish larva tail amputation model was used to assess immune cell migration.
Main Results:
- BIM nanoparticles significantly alleviated joint swelling in the MSU-induced arthritis mouse model.
- Treatment abrogated ROS and inflammatory cytokine secretions, reducing neutrophil infiltration and fluid buildup.
- Nanoparticles reduced macrophage and neutrophil influx in various inflammation models by blocking and inducing reverse migration.
Conclusions:
- Biomineralized nanoscavengers offer a promising strategy for treating gouty arthritis.
- Dual blockade of peroxides and COX2 by BIM nanoscavengers effectively prevents inflammatory cell influx at inflammation sites.
