In vivo anticancer evaluation of the hyperthermic efficacy of anti-human epidermal growth factor receptor-targeted PEG-based nanocarrier containing magnetic nanoparticles

Giovanni Baldi,¹ Costanza Ravagli,¹ Filippo Mazzantini,¹ George Loudos,² Jaume Adan,³ Marc Masa,³ Dimitrios Psimadas,² Eirini A Fragogeorgi,² Erica Locatelli,⁴ Claudia Innocenti,^5,6 Claudio Sangregorio,^5,7 Mauro Comes Franchini<sup>4

1</sup>CERICOL, Sovigliana-Vinci, Italy; ²Technological Educational Institute of Athens, Athens, Greece; ³Leitat Technological Center, Barcelona, Spain; ⁴Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, ⁵Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), ⁶Dipartimento di Chimica U Schiff, Università di Firenze, Firenze, ⁷Centro Nazionale delle Ricerche (ICCOM – CNR), Firenze, Italy

Abstract: Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer. Here we report the chemical synthesis and characterization of a poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-based nanocarrier containing iron oxide nanoparticles and human epithelial growth factor receptor on the outer shell. The nanocarrier was also radiolabeled with ^99mTc and tested as a theranostic nanomedicine, ie, it was investigated for both its diagnostic ability in vivo and its therapeutic hyperthermic effects in a standard A431 human tumor cell line. Following radiolabeling with ^99mTc, the biodistribution and therapeutic hyperthermic effects of the nanosystem were studied noninvasively in vivo in tumor-bearing mice. A substantial decrease in tumor size correlated with an increase in both nanoparticle concentration and local temperature was achieved, confirming the possibility of using this multifunctional nanosystem as a therapeutic tool for epidermoid carcinoma.

Keywords: magnetic nanoparticles, polymeric nanocarriers, skin cancer, hyperthermia, single-photon emission computed tomography, imaging

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