Transition Metal-Based Prodrugs for Anticancer Drug Delivery

Transition metal complexes, of which the platinum(II) complex cisplatin is an example, have been used in medicine to treat cancer for more than 40 years. Although many successes have been achieved, there are problems associated with the use of these drugs, such as side effects and drug resistance. Converting them into prodrugs, to make them more inert, so that they can travel to the tumour site unchanged and release the drug in its active form only there, is a strategy which is the subject of much research nowadays. The new prodrugs may be activated and release the cytotoxic agent by differences in oxygen concentration or in pH, by the action of overexpressed enzymes, by differences in metabolic rates, etc., which characteristically distinguish cancer cells from normal ones, or even by the input of radiation, which can be visible light. Converting a metal complex into a prodrug may also be used to improve its pharmacological properties. In some cases, the metal complex is a carrier which transports the active drug as a ligand. Some platinum prodrugs have reached clinical trials. So far platinum, ruthenium and cobalt have been the most studied metals. This review presents the recent developments in this area, including the types of complexes used, the mechanisms of drug action and in some cases the techniques applied to monitor drug delivery to cells.