Folate receptor-targeted dendrimer-methotrexate conjugate for inflammatory arthritis

Rong Qi, Istvan Majoros, Asish C. Misra, Alisa E. Koch, Phil Campbell, Hubert Marotte, Ingrid L. Bergin, Zhengyi Cao, Sascha Goonewardena, Jingga Morry, Shuai Zhang, Michael Beer, Paul Makidon, Alina Kotlyar, Thommey P. Thomas, James R. Baker

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages. These cells are thought to play an important role in the development of RA. With G5 serving as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to activated macrophages were assessed in RAW264.7, NR8383 and primary rat peritoneal macrophages. The results indicated that the binding of either conjugate to macrophages was concentration- and temperature-dependent and could be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored on an adjuvant-induced inflammatory arthritis model and had similar preventive effects in inflammatory arthritis at a MTX equivalent dose of 4.95 -mol/kg. These studies indicated that when multiples of MTX are conjugated on dendritic polymers, they specifically bind to folate receptor overexpressing macrophages and have comparable anti-inflammatory effects to folate targeted MTX conjugated polymers.

Original languageEnglish (US)
Pages (from-to)1370-1384
Number of pages15
JournalJournal of Biomedical Nanotechnology
Issue number8
StatePublished - Aug 1 2014
Externally publishedYes


  • Dendrimer-Methotrexate conjugates
  • Folate receptor
  • Folic acid
  • Inflammatory arthritis.
  • Macrophages

ASJC Scopus subject areas

  • General Medicine


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