Binding of doxorubicin (DOX) immobilized on nanodispersed magnetite (DOX-M conjugates with loading in the range of 0.16-25.1 mg DOX/g carrier) to intact human erythrocytes in concurrence with free DOX was investigated. Two specific binding sites for doxorubicin were revealed at the plasma membrane of human erythrocytes. Changes in the ordering of the DOX-M nanoparticles according to small angle scattering data are consistent with their specific binding at the plasma membrane upon incubation with erythrocytes. Free and conjugated doxorubicin modulated signal transduction in erythrocytes in a similar way. Both up-regulate nitric oxide and cyclic GMP and down-regulate cyclic AMP production and stabilize the membranes of oxidatively damaged erythrocytes.
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