Targeting of Nanoparticles: Folate Receptor
Nanoparticulate medicines offer the advantage of allowing delivery of large quantities of unmodified drug within the same particle. Nanoparticle uptake by cancer cells can, however, be compromised due to the large size and hydrophilicity of the particle. To circumvent cell penetration problems and simultaneously improve tumor specificity, nanoparticulate medicines have been linked to targeting ligands that bind to malignant cell surfaces and enter cells by receptor-mediated endocytosis. In this chapter, we summarize multiple methods for delivering nanoparticles into cancer cells by folate receptor-mediated endocytosis, devoting special emphasis to folate-targeted liposomes. Folate receptor-mediated endocytosis has emerged as an attractive strategy for nanoparticle delivery due to both overexpression of the folate receptor on cancer cells and the rapid internalization of the receptor by receptor-mediated endocytosis.
Key wordsFolate receptor-targeted drugs cancer nanomedicines ligand-targeted nanoparticles folate-targeted imaging agents folic acid coupling chemistries pteroic acid synthesis conjugation of amine, hydroxyl, thiol, or carboxyl functionalized nanoparticles to folate
- 8.Park, E. K., Lee, S. B., and Lee, Y. M. (2005) Preparation and characterization of methoxypoly(ethylene glycol)/poly(epsilon-caprolactone) amphiphilic block copolymeric nanospheres for tumor-specific folate-mediated targeting of anticancer drugs. Biomaterials 26, 1053–1061.CrossRefPubMedGoogle Scholar
- 31.Xu, L., Vlahov, I. R., Leamon, C. P., Santhapuram, H., and Li, C. (2006) Synthesis and purification of pteroic acid and conjugates thereof. US Patent WO2006101845.Google Scholar
- 35.Vlahov, I. R., Santhapuram, H. R., Kleindl, P. J., Howard, S. J., Stanford, K. M., and Leamon, C. P. (2006) Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part 1: EC 145, a folic acid conjugate of desacetylvinblastine monohydrazide. Bioorg Med Chem Lett 16, 5093–5096.CrossRefPubMedGoogle Scholar