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

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Abstract

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–Fe2+ 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.

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Acknowledgments

This study was supported in part by grants from the Ligue Nationale contre le Cancer (Comités Indre-et-Loire, Loir-et-Cher, Indre), France and from the Region Centre, France (NANOMAG Project).

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Authors and Affiliations

  1. Université François-Rabelais, EA 4244 «Physico-Chimie des Matériaux et des Biomolécules», Groupe thématique «Nanovecteurs Magnétiques pour la Chimiothérapie», Tours, 37200, France

    E. Munnier, S. Cohen-Jonathan, K. Hervé, C. Linassier, M. Soucé, P. Dubois & I. Chourpa

  2. Institut Fédératif de Recherche 135 “Imagerie Fonctionnelle”, Tours, 37000, France

    E. Munnier, S. Cohen-Jonathan, K. Hervé, C. Linassier, M. Soucé, P. Dubois & I. Chourpa

  3. CHRU Bretonneau, Service d’Oncologie Médicale, Tours, 37000, France

    C. Linassier

  4. Laboratoire de Pharmacie Galénique, UFR de Pharmacie, 31 avenue Monge, 37200, Tours, France

    E. Munnier

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  1. E. Munnier
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  2. S. Cohen-Jonathan
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  3. K. Hervé
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  4. C. Linassier
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  6. P. Dubois
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  7. I. Chourpa
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Correspondence to E. Munnier.

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Munnier, E., Cohen-Jonathan, S., Hervé, K. et al. Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity. J Nanopart Res 13, 959–971 (2011). https://doi.org/10.1007/s11051-010-0093-1

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  • DOI: https://doi.org/10.1007/s11051-010-0093-1

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