Carboplatin as an alternative to Cisplatin in chemotherapies: New insights at single molecule level

L.Oliveira, J.M.Caquito Jr, M.S. Rocha

Here we report a new study performed at single molecule level on the interaction of the antineoplastic drug Carboplatin and the DNA molecule - the main target of the drug inside cells in cancer chemotherapies. By using optical tweezers, we measure how the mechanical properties of the DNA-Carboplatin complexes changes as a function of the drug concentration in the sample, for two different ionic strengths ([Na] = 150 mM and [Na] = 1 mM). From these measurements, the binding mechanism and the physicochemical (binding) parameters of the interaction were inferred and directly compared to those obtained for the precursor drug Cisplatin under equivalent conditions. As the main conclusion, we show that Carboplatin binds preferentially forming covalent monoadducts in contrast to Cisplatin, which is hydrolyzed easier and presents a higher efficiency in forming covalent diadducts along the double-helix. In addition, we explicitly show that Carboplatin is much less sensitive to ionic strength changes when compared to Cisplatin. These findings provide new insights on the interactions of platinum-based compounds with the DNA molecule, being important to improve the current treatments and in the development of new antineoplastic agents.

DOI