Effect of receptor occupancy on folate receptor internalization

N. Achini Bandara, Michael J. Hansen, Philip S. Low

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The folate receptor (FR) is a GPI anchored cell surface glycoprotein that functions to facilitate folic acid uptake and mediate signal transduction. With the introduction of multiple folate-targeted drugs into the clinic, the question has arisen regarding how frequently a patient can be dosed with a FR-targeted drug or antibody and whether dosing frequency exerts any impact on the availability of FR for subsequent rounds of FR-mediated drug uptake. Although the rate of FR recycling has been examined in murine tumor models, little or no information exists on the impact of FR occupancy on its rate of endocytosis. The present study quantitates the number of cell surface FR-α and FR-β following exposure to saturating concentrations of a variety of folate-linked molecules and anti-FR antibodies, including the unmodified vitamin, folate-linked drug mimetics, multifolate derivatized nanoparticles, and monoclonal antibodies to FR. We report here that FR occupancy has no impact on the rate of FR internalization. We also demonstrate that multivalent conjugates that bind and cross-link FRs at the cell surface internalize at the same rate as monovalent folate conjugates that have no impact on FR clustering, even though the multivalent conjugates traffic through a different endocytic pathway.

Original languageEnglish (US)
Pages (from-to)1007-1013
Number of pages7
JournalMolecular pharmaceutics
Issue number3
StatePublished - Mar 3 2014


  • antibodies to folate receptors
  • folate receptor endocytosis
  • ligand targeted drugs
  • ligand valency on nanomedicines
  • receptor recycling

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery


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