Abonnement à la biblothèque: Guest
Portail numérique Bibliothèque numérique eBooks Revues Références et comptes rendus Collections
Critical Reviews™ in Therapeutic Drug Carrier Systems
Facteur d'impact: 2.9 Facteur d'impact sur 5 ans: 3.72 SJR: 0.736 SNIP: 0.551 CiteScore™: 2.43

ISSN Imprimer: 0743-4863
ISSN En ligne: 2162-660X

Volumes:
Volume 37, 2020 Volume 36, 2019 Volume 35, 2018 Volume 34, 2017 Volume 33, 2016 Volume 32, 2015 Volume 31, 2014 Volume 30, 2013 Volume 29, 2012 Volume 28, 2011 Volume 27, 2010 Volume 26, 2009 Volume 25, 2008 Volume 24, 2007 Volume 23, 2006 Volume 22, 2005 Volume 21, 2004 Volume 20, 2003 Volume 19, 2002 Volume 18, 2001 Volume 17, 2000 Volume 16, 1999 Volume 15, 1998 Volume 14, 1997 Volume 13, 1996 Volume 12, 1995

Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v15.i6.20
41 pages

Folate-Mediated Targeting of Therapeutic and Imaging Agents to Cancers

Joseph A. Reddy
Department of Chemistry, Purdue University, West Lafayette, IN 47907-1393
Philip S. Low
Department of Chemistry, Purdue University, West Lafayette, IN 47907-1393

RÉSUMÉ

The vitamin folic acid (FA) enters cells either through a carrier protein, termed the reduced folate carrier, or via receptor-mediated endocytosis facilitated by the folate receptor (FR). Because folate-drug conjugates are not substrates of the former, they penetrate cells exclusively via FR-mediated endocytosis. When FA is covalently linked via its γ-carboxyl to a drug or imaging agent, FR binding affinity (KD ~ 10−10 M) is not measurably compromised, and endocytosis proceeds relatively unhindered, promoting uptake of the attached drug/imaging agent by the FR-expressing cell. Because FRs are significantly overexpressed on a large fraction of human cancer cells (e.g., ovarian, lung, breast, endometrial, renal, colon, and cancers of myeloid hematopoietic cells), this methodology may allow for the selective delivery of a wide range of imaging and therapeutic agents to tumor tissue. Folate-mediated tumor targeting has been exploited to date for delivery of the following molecules and molecular complexes: (i) protein toxins, (ii) low-molecular-weight chemotherapeutic agents, (iii) radioimaging agents, (iv) MRI contrast agents, (v) radiotherapeutic agents, (vi) liposomes with entrapped drugs, (vii) genes, (viii) antisense oligonucleotides, (ix) ribozymes, and (x) immunotherapeutic agents. In virtually all cases, in vitro studies demonstrate a significant improvement in potency and/or cancer-cell specificity over the nontargeted form of the same pharmaceutical agent. Where live animal studies have been conducted, they also reveal significant promise.