Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 13; no. 3; pp. 959 - 971
• Main Authors: Munnier, E., Cohen-Jonathan, S., Hervé, K., Linassier, C., Soucé, M., Dubois, P., Chourpa, I.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2011; Springer Nature B.V; Springer Verlag
• Subjects: Analytical chemistry; Atomic absorption spectroscopy; Binding; Cancer; Characterization and Evaluation of Materials; Chemical Sciences; Chemistry and Materials Science; Cytotoxicity; Doxorubicin; Drugs; Imaging; In vitro testing; Inorganic Chemistry; INT; Iron oxides; Lasers; Life Sciences; Light microscopy; Materials Science; Medication; Nanoparticles; Nanotechnology; Optical Devices; Optics; Pharmaceutical sciences; Photonics; Physical Chemistry; Research Paper; Side effects; Spectral analysis; Cytotoxicity; MCF-7 cells; Confocal spectral imaging; Doxorubicin; Nanomedicine; Magnetic drug targeting
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-010-0093-1

The clinical use of the anticancer drug doxorubicin (DOX) is limited by strong side effects and phenomena of cell resistance. Drug targeting by binding DOX to nanoparticles could overcome these limitations. We recently described a method to associate DOX to superparamagnetic iron oxide nanoparticles (SPION) in view of magnetic drug targeting (Munnier et al. in Int J Pharm 363:170–176, 2008 ). DOX is bound to the nanoparticle surface through a pre-formed DOX–Fe 2+ complex. The DOX-loaded SPION present interesting properties in terms of drug loading and biological activity in vitro. The purpose of this study is to explore the possible mechanisms of the in vitro cytotoxicity of DOX-loaded SPION. The uptake of SPION was followed qualitatively by conventional optical microscopy after Prussian blue staining and quantitatively by iron determination by atomic absorption spectroscopy. The subcellular distribution of intrinsically fluorescent DOX was followed by confocal spectral imaging (CSI) and the subsequent cytotoxicity by the MTT method. We reveal modifications of DOX intracellular interactions for SPION-delivered drug and increased cytotoxicity. These results are discussed in terms of internalization route of the drug and of a potential role of iron oxide nanoparticles in the observed cytotoxicity.