Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation.

Published

Journal Article

Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.

Full Text

Cited Authors

  • Liang, H; Peng, B; Dong, C; Liu, L; Mao, J; Wei, S; Wang, X; Xu, H; Shen, J; Mao, H-Q; Gao, X; Leong, KW; Chen, Y

Published Date

  • October 16, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 4291 -

PubMed ID

  • 30327464

Pubmed Central ID

  • 30327464

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-06603-5

Language

  • eng