Targeted drug delivery via the folate receptor

Adv Drug Deliv Rev. 2000 Mar 30;41(2):147-62. doi: 10.1016/s0169-409x(99)00062-9.

Abstract

The folate receptor is a highly selective tumor marker overexpressed in greater than 90% of ovarian carcinomas. Two general strategies have been developed for the targeted delivery of drugs to folate receptor-positive tumor cells: by coupling to a monoclonal antibody against the receptor and by coupling to a high affinity ligand, folic acid. First, antibodies against the folate receptor, including their fragments and derivatives, have been evaluated for tumor imaging and immunotherapy clinically and have shown significant targeting efficacy in ovarian cancer patients. Folic acid, a high affinity ligand of the folate receptor, retains its receptor binding properties when derivatized via its gamma-carboxyl. Folate conjugation, therefore, presents an alternative method of targeting the folate receptor. This second strategy has been successfully applied in vitro for the receptor-specific delivery of protein toxins, anti-T-cell receptor antibodies, interleukin-2, chemotherapy agents, gamma-emitting radiopharmaceuticals, magnetic resonance imaging contrast agents, liposomal drug carriers, and gene transfer vectors. Low molecular weight radiopharmaceuticals based on folate conjugates showed much more favorable pharmacokinetic properties than radiolabeled antibodies and greater tumor selectivity in folate receptor-positive animal tumor models. The small size, convenient availability, simple conjugation chemistry, and presumed lack of immunogenicity of folic acid make it an ideal ligand for targeted delivery to tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / analysis
  • Carrier Proteins / physiology*
  • Drug Carriers
  • Drug Delivery Systems*
  • Folate Receptors, GPI-Anchored
  • Genetic Therapy
  • Humans
  • Immunotoxins / therapeutic use
  • Liposomes
  • Neoplasms / therapy
  • Radioimmunodetection
  • Radioimmunotherapy
  • Receptors, Cell Surface*

Substances

  • Carrier Proteins
  • Drug Carriers
  • Folate Receptors, GPI-Anchored
  • Immunotoxins
  • Liposomes
  • Receptors, Cell Surface