CHARACTERIZATION OF THE INTERACTION OF DOXORUBICIN WITH (POLY)PHOSPHOINOSITIDES IN MODEL SYSTEMS - EVIDENCE FOR SPECIFIC INTERACTION WITH PHOSPHATIDYLINOSITOL-MONOPHOSPHATE AND PHOSPHATIDYLINOSITOL-DIPHOSPHATE

The anticancer drug doxorubicin penetrates into Langmuir monolayers containing phosphoinositides. Upon binding of doxorubicin to phosphoinositide-containing SUV, its fluorescence is self-quenched due to self-association. As compared to other anionic phospholipids, as much as 2- to 3-fold larger effects were obtained with PIP and PIP2, in mixtures of these lipids with DOPC. Doxorubicin competes efficiently with the non-penetrating antibiotic neomycin for binding to PIP2. According to its penetration, specific binding of doxorubicin was half-maximal at 5-15-mu-M. It is likely that also in biological membranes doxorubicin binds specifically to PIP and PIP2.