Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis

Roun Heo, Dong Gil You, Wooram Um, Ki Young Choi, Sangmin Jeon, Jong Sung Park, Yuri Choi, Seunglee Kwon, Kwang Meyung Kim, Ick Chan Kwon, Dong Gyu Jo, Young Mo Kang, Jae Hyung Park

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

With the aim of developing nanoparticles for targeted delivery of methotrexate (MTX) to inflamed joints in rheumatoid arthritis (RA), an amphiphilic polysaccharide was synthesized by conjugating 5β-cholanic acid to a dextran sulfate (DS) backbone. Due to its amphiphilic nature, the DS derivative self-assembled into spherical nanoparticles (220 nm in diameter) in aqueous conditions. The MTX was effectively loaded into the DS nanoparticles (loading efficiency: 73.0%) by a simple dialysis method. Interestingly, the DS nanoparticles were selectively taken up by activated macrophages, which are responsible for inflammation and joint destruction, via scavenger receptor class A-mediated endocytosis. When systemically administrated into mice with experimental collagen-induced arthritis (CIA), the DS nanoparticles effectively accumulated in inflamed joints (12-fold more than wild type mice (WT)), implying their high targetability to RA tissues. Moreover, the MTX-loaded DS nanoparticles exhibited significantly improved therapeutic efficacy against CIA in mice compared to free MTX alone. Overall, the data presented here indicate that DS nanoparticles are potentially useful nanomedicines for RA imaging and therapy.

Original languageEnglish
Pages (from-to)15-26
Number of pages12
JournalBiomaterials
Volume131
DOIs
Publication statusPublished - 2017 Jul 1
Externally publishedYes

Keywords

  • Dextran sulfate
  • Drug delivery
  • Macrophage
  • Nanoparticles
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Heo, R., You, D. G., Um, W., Choi, K. Y., Jeon, S., Park, J. S., Choi, Y., Kwon, S., Kim, K. M., Kwon, I. C., Jo, D. G., Kang, Y. M., & Park, J. H. (2017). Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis. Biomaterials, 131, 15-26. https://doi.org/10.1016/j.biomaterials.2017.03.044