Effect of a kosmotropic ion on doxorubicin self-assembly and interaction with biomimetic systems

摘要

Ions of the Hofmeister series alter water structure. Kosmotropes (e.g. sulfate) increase, while chaotropes decrease water structure. Hofmeister ions modulate various properties, such as the solubility and the partitioning of solutes between water and organic solvents and into model membranes. The effect of the kosmotropic ion sulfate on the self-assembly and interaction of the anticancer drug doxorubicin (DOXO) with lipid bilayers was studied by employing fluorescence spectroscopy. As expected, sulfate decreased DOXO's water solubility. In the absence of sulfate, DOXO binds more strongly to large unilamellar vesicles of the anionic phospholipid dioleoyl phosphatidylglycerol (DOPG) than to large unilamellar vesicles of the zwitterionic phospholipid dioleoyl phosphatidylcholine (DOPC). While increasing sulfate concentrations promoted increased DOXO binding to DOPC, the addition of salt caused an initial decrease in drug binding to DOPG, followed by an increase at higher sulfate concentrations. The results indicate that water structure effects prevail in the effect of sulfate upon DOXO solubility and partitioning into DOPC bilayers, whereas a more complex series of events contributes to the observed effect of the ion on the partitioning of the drug into DOPG bilayers.