THE INTERACTION OF THE ANTICANCER DRUG CISPLATIN WITH PHOSPHOLIPIDS IS SPECIFIC FOR NEGATIVELY CHARGED PHOSPHOLIPIDS AND RAKES PLACE AT LOWCHLORIDE-ION CONCENTRATION

The interaction of the anti-cancer drug cis-diamminedichloroplatinum(I I) (cisPt) with model membranes was studied, with emphasis on the cisP t and phospholipid species involved. Binding studies using large unila mellar vesicles have revealed that: (i) Interaction involved negativel y charged phospholipids only, and (ii) Interaction with negatively cha rged phospholipids was observed only in buffers with low Cl- concentra tion, indicating that aquated, positively charged cisPt is involved. B inding to all negatively charged phospholipids tested was highest at p H 6.0. At pH 7.4 a high and specific binding was observed with phospha tidic acid and phosphatidylserine. The consequences of cisPt binding o n the organization of lipids was investigated with differential scanni ng calorimetry studies. These studies have indicated a higher ordering of dispersions of negatively charged phospholipids in the presence of divalent cationic cisPt. Summarizing, the interaction of positively c harged cisPt species with negatively charged phospholipids is signific ant and should be considered in in vivo experiments.