Platinum Drug Distribution in Cancer Cells and Tumors

Some of the significant advancements made in the understanding of the way platinum drugs enter and exit cells are discussed. Efforts have also been made to understand the intracellular behavior and distribution of these drugs, along with the way these considerations relate to tumors. The increasing number of techniques for monitoring platinum drug accumulation are discussed. Cisplatin is highly polar and cellular accumulation occurs at a slower rate than other small-molecule anticancer drug. The complex exists in its neutral and intact form in blood plasma, due to suppression of aquation by the high concentration of chloride ions. The nature of the leaving groups affects the biodistribution and toxicity of the complex in the case of platinum(II) cisplatin analogues. The nonleaving groups influence the nature of the DNA adducts formed, while in vivo reduction is accompanied by the loss of two additional axial ligands in the case of platinum(IV) complexes.