Dr. Baker has applied for a patent for the use of methotrexate-conjugated dendrimer (G5-FA-MTX) as a therapeutic drug for inflammatory arthritis.
Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis
Article first published online: 31 AUG 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 9, pages 2671–2680, September 2011
How to Cite
Thomas, T. P., Goonewardena, S. N., Majoros, I. J., Kotlyar, A., Cao, Z., Leroueil, P. R. and Baker, J. R. (2011), Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis & Rheumatism, 63: 2671–2680. doi: 10.1002/art.30459
- Issue published online: 31 AUG 2011
- Article first published online: 31 AUG 2011
- Accepted manuscript online: 26 MAY 2011 01:45PM EST
- Manuscript Accepted: 12 MAY 2011
- Manuscript Received: 13 OCT 2010
- NIH. Grant Numbers: 1-R33-CA-112141, 1-R21-RR-021893
- National Cancer Institute. Grant Number: P30-AR-048310
- Rheumatic Disease Core Center at the University of Michigan. Grant Number: R01-EB-005028
- National Institute of Biomedical Imaging and Bioengineering
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.
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.
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.
The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.