Interactions of Mitoxantrone-Modified Superparamagnetic Iron Oxide Nanoparticles with Biomimetic Membranes and Cells

We report on the formation of conjugates of superparamagnetic iron nanoparticles (NPs) with the chemotherapeutic agent mitroxantrone (MTX). The NPs are synthesized from mixed iron oxides and are ca. 15 nm in diameter. Decoration of the NP surface with MTX is accomplished with standard coupling chemistry techniques using sebacic acid as the coupling agent. The resulting NP-MTX conjugate is characterized thermogravimetrically, spectroscopically and electrochemically. The interactions of the NP-MTX conjugate with a model lipid layer formed as a Langmuir-Blodgett (LB) film reveal that the nanoparticle exhibits a significant perturbative effect on the layer, as seen from translational diffusion (FRAP) measurements. Evaluation of the cytotoxicity of the conjugate relative to that of free MTX demonstrates that the NP-MTX conjugate is more toxic than free MTX for both normal and malignant cell lines. These results underscore the importance of targeted delivery in the administration of chemotherapeutic agents.