title: Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis.
abstract: OBJECTIVE
  To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA- and methotrexate (MTX)-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis.
  
  
  METHODS
  In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence-tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX.
  
  
  RESULTS
  Folate-targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor β-expressing macrophage cell lines and primary mouse macrophages. The conjugate G5-FA-MTX acted as a potent antiinflammatory agent and reduced arthritis-induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease.
  
  
  CONCLUSIONS
  The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Thommey P
authors: TP
authors: Thomas
authors: Sascha N
authors: SN
authors: Goonewardena
authors: Istvan J
authors: IJ
authors: Majoros
authors: Alina
authors: A
authors: Kotlyar
authors: Zhengyi
authors: Z
authors: Cao
authors: Pascale R
authors: PR
authors: Leroueil
authors: James R
authors: JR
authors: Baker
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