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Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

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Abstract

Currently, sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients. Unfortunately, its side effects, particularly its overall toxicity, limit the therapeutic response that can be achieved. Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field, thus improving intratumoral accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by complementary techniques. This nanovector system provided effective drug delivery, had an average hydrodynamic diameter of about 125 nm, had good stability in aqueous medium, and allowed controlled drug loading. Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle. An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver. Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. These experiments demonstrated that this delivery platform is able to enhance sorafenib’s antitumor effectiveness by magnetic targeting. The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites, where selective release of sorafenib can improve its efficacy and safety profile.

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Acknowledgements

The University of Bari (Italy) and the Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems (C.I.R.C.M.S.B.) are gratefully acknowledged for their financial support. The work has been also supported by Nanomax-integrable sensors for pathological biomarkers diagnosis (N-CHEM) and NANOfotocatalizzatori per un’Atmosfera più PULita (NANOAPULIA) projects.

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Authors and Affiliations

  1. Istituto per i Processi Chimico-Fisici-CNR UOS Bari, Via Orabona 4, 70125, Bari, Italy

    Nicoletta Depalo, Marinella Striccoli & Maria Lucia Curri

  2. Istituto Tumori IRCCS Giovanni Paolo II, viale O. Flacco 65, 70124, Bari, Italy

    Rosa Maria Iacobazzi, Letizia Porcelli & Amalia Azzariti

  3. Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70125, Bari, Italy

    Gianpiero Valente & Elisabetta Fanizza

  4. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Via Orabona 4, 70125, Bari, Italy

    Ilaria Arduino, Valentino Laquintana, Annalisa Cutrignelli, Angela Lopedota, Massimo Franco & Nunzio Denora

  5. Dipartimento di Chimica e Chimica Industriale, Università di Genova, Via Dodecaneso 31, 16146, Genova, Italy

    Silvia Villa & Fabio Canepa

Authors
  1. Nicoletta Depalo
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  2. Rosa Maria Iacobazzi
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  3. Gianpiero Valente
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  7. Valentino Laquintana
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  8. Elisabetta Fanizza
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  10. Annalisa Cutrignelli
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  11. Angela Lopedota
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  16. Nunzio Denora
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Correspondence to Nunzio Denora.

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Depalo, N., Iacobazzi, R.M., Valente, G. et al. Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma. Nano Res. 10, 2431–2448 (2017). https://doi.org/10.1007/s12274-017-1444-3

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  • DOI: https://doi.org/10.1007/s12274-017-1444-3

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