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Adv Drug Deliv Rev. 2004 Apr 29;56(8):1205-17.

Folate receptor-mediated targeting of therapeutic and imaging agents to activated macrophages in rheumatoid arthritis.

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  • 1Department of Chemistry, 560 Oval Drive, 1393 Brown Bldg., Purdue University, West Lafayette, IN 47907, USA.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the joints and destruction of cartilage and bone, often compromising both the quality and duration of life. The disease pathology is complex, involving the infiltration and activation of various populations of immune cells along with the release of destructive inflammatory mediators into the synovium of affected joints. Although it is still debatable whether activated macrophages are the primary promoters of RA, emerging data clearly show that the biological activity of this subset of inflammatory cells greatly contributes to both the acute and chronic stages of the disease. The further discovery of folate receptor expression on these activated (but not quiescent) macrophages in both animal models and human patients with naturally occurring RA has opened the possibility of exploiting folic acid to target attached drugs to this population of pathologic cells. Indeed, recent studies have shown that folate-linked imaging and therapeutic agents can be selectively delivered to arthritic joints, allowing both visualization and treatment of RA, with little or no collateral toxicity to normal tissues. This review will first summarize data documenting specific expression of the folate receptor on activated macrophages and then focus on the development of folate-targeted diagnostic and therapeutic agents for guided intervention into rheumatoid arthritis.

PMID:
15094216
DOI:
10.1016/j.addr.2004.01.012
[PubMed - indexed for MEDLINE]
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