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X-Ray Reflectivity and Diffraction Studies of Doxorubicin Binding to Model Lipid Membranes

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The effect of anticancer antibiotic doxorubicin on structural organization of anionic lipid monolayers has been studied. X-ray reflectivity and grazing incidence diffraction techniques were applied to monitor the changes in 2D structure and electron density distribution of Langmuir monolayer composed of negatively charged dipalmitoylphosphatidylglycerol (DPPG) and dioleoylphosphatidylserine (DOPS). For comparison, monolayer of zwitterionic dipalmitoylphosphatidylethanolamine (DPPE) also was investigated. The presented experimental results suggest that doxorubicin interaction with anionic lipid monolayers (DPPG and DOPS) proceeds preferentially via electrostatic attraction—positively charged amino groups of doxorubicin bind to negatively charged head groups of phospholipid molecules. Based on the obtained data, the penetration of doxorubicin into the hydrophobic part of anionic lipid monolayers does not occur. X-ray measurements on DPPE monolayer indicated that doxorubicin did not cause any significant alterations of molecular packing in condensed monolayer of zwitterionic DPPE molecules.

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The data analysis was supported in part by the State Assignment FSRC “Crystallography and Photonics”, Russian Academy of Sciences. We acknowledge the European Synchrotron Radiation Facility for provision of the beam time at ID10 beam line. The authors are also grateful to an anonymous referee for the valuable comments and advice.


This work was supported in part by the Russian Foundation of Basic Research (project No 19-515-06008).

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Correspondence to Natalia Novikova.

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Novikova, N., Kovalchuk, M., Konovalov, O. et al. X-Ray Reflectivity and Diffraction Studies of Doxorubicin Binding to Model Lipid Membranes. BioNanoSci. 10, 618–624 (2020).

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