Interactions of anticancer drugs with model lipid membranes - determination of the mechanisms and interfacial stoichiometry.
Doxorubicin (DOx) is a widely used anticancer drug. Despite numerous studies, there is still confusion concerning the exact mechanisms of the intercalation of the drug into the monolayer. We have recently investigated the interactions of DOx (positively charged) with model membranes at the air-water interface. In recent experiments on FIGARO, we have demonstrated the importance of electrostatic interactions between the drug and monolayers at 10 mN/m: the best model fit that describes the data recorded on (negative) DMPS is that with the drug mixed only with head groups while the interaction between the drug and (zwitterionic) DMPC was below the detection limit. As a continuation, we propose to resolve: (1) the location of DOx in DMPS monolayers at a higher surface pressure, (2) the dynamic interfacial stoichiometry during compression/expansion cycles for the DOx/DMPS and DOx/DMPC systems, (3) the effects of DMPC on the specific interaction of DOx in mixed DMPS:DMPC monolayers of different ratios. This work represents a step towards the study of more biologically relevant systems, and can lead to a better understanding of the interactions of anticancer drugs with model membranes.
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MATYSZEWSKA Dorota; Richard A. Campbell; GUTFREUND Philipp; Armando Maestro; NAZARUK Ewa and TUMMINO Andrea. (2018). Interactions of anticancer drugs with model lipid membranes - determination of the mechanisms and interfacial stoichiometry.. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-02-805
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