Targeting Activated Macrophages Via a Functional Folate Receptor for Potential Treatment of Autoimmune/Inflammatory Disorders

Abstract

The folate receptor expressed by activated macrophages associated with chronic inflammation is fully functional in binding/internalization of high-affinity folate ligands. The recent effort in developing folate-targeted anti-macrophage therapies has yielded some encouraging results. However, the challenges lie not so much in finding the right ligand, but rather its multifaceted nature in identifying suitable intracellular targets, finding highly potent base drugs, design of appropriate linker chemistry, and choosing "realistic" inflammation models to demonstrate efficacy and target specificity. In this chapter we will provide background for this complex topic and discuss the rationale for finding a balance in these specific areas of interest.