Title:Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry
Volume: 25
Issue: 23
Author(s): Pauraic Mc Carron, Aisling Crowley, Denis O’Shea, Malachy McCann, Orla Howe, Mary Hunt and Michael Devereux*
Affiliation:
- The Centre for Biomimetic & Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8,Ireland
Keywords:
Metal-folate complexes, folate receptor-targeted drug delivery, chemotherapeutics, diagnostics, DHFR.
Abstract: The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells,
coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent
elucidation of the folate receptor’s overexpression in specific cancer cell types; heralded the arrival of the
area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule
drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such
as cancer, is well established. The application of inorganic folate-targeted drugs offers significant potential
to expand and enhance this therapeutic approach. From the data made available to date, it is apparent that
this aspect of inorganic medicinal chemistry is in its youth but has the capability to contribute greatly to
cancer research, both in therapy and diagnosis. The union of folate-receptor targeting and inorganic
medicine may also lead to the development of treatments for disorders such as chronic-inflammation,
tuberculosis, neurodegenerative disease and leishmaniasis. In this review, we summarize what is known
about the coordination chemistry of folic acid and the therapeutic potential of such complexes. We also
describe approaches adopted to conjugate platinum drugs to folate- or folate-carrier- systems and their
prospective ability to overcome problems associated with unwanted side-effects and resistance by improving
their delivery and/or selectivity. The literature pertaining to non-platinum metal complex conjugates
with folic acid is also reviewed revealing that this is an area that offers significant potential to develop targeted
therapeutic approaches in areas such as chemotherapy and molecular imaging for diagnostics.