Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis

Nat Nanotechnol. 2018 Dec;13(12):1182-1190. doi: 10.1038/s41565-018-0254-4. Epub 2018 Sep 3.

Abstract

Rheumatoid arthritis is a common chronic inflammatory disorder and a major cause of disability. Despite the progress made with recent clinical use of anti-cytokine biologics, the response rate of rheumatoid arthritis treatment remains unsatisfactory, owing largely to the complexity of cytokine interactions and the multiplicity of cytokine targets. Here, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy for rheumatoid arthritis management. By fusing neutrophil membrane onto polymeric cores, we prepare neutrophil membrane-coated nanoparticles that inherit the antigenic exterior and associated membrane functions of the source cells, which makes them ideal decoys of neutrophil-targeted biological molecules. It is shown that these nanoparticles can neutralize proinflammatory cytokines, suppress synovial inflammation, target deep into the cartilage matrix, and provide strong chondroprotection against joint damage. In a mouse model of collagen-induced arthritis and a human transgenic mouse model of arthritis, the neutrophil membrane-coated nanoparticles show significant therapeutic efficacy by ameliorating joint damage and suppressing overall arthritis severity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / therapy
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy*
  • Cell Membrane / chemistry
  • Cell Membrane / immunology*
  • Cell Membrane / transplantation
  • Cytokines / immunology
  • Disease Models, Animal
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / therapy*
  • Joints / immunology
  • Joints / pathology
  • Male
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Nanomedicine
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Neutrophils / chemistry
  • Neutrophils / immunology*

Substances

  • Cytokines