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Cetuximab-conjugated iron oxide nanoparticles for cancer imaging and therapy

Authors Tseng SH, Chou MY, Chu IM

Received 31 December 2014

Accepted for publication 18 March 2015

Published 20 May 2015 Volume 2015:10(1) Pages 3663—3685

DOI https://doi.org/10.2147/IJN.S80134

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Shih-Heng Tseng,1,2 Min-Yuan Chou,2 I-Ming Chu1

1Department of Chemical Engineering, National Tsing Hua University, 2Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan

Abstract: We have developed a theranostic nanoparticle, ie, cet-PEG-dexSPIONs, by conjugation of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody, cetuximab, to dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) via periodate oxidation. Approximately 31 antibody molecules were conjugated to each nanoparticle. Cet-PEG-dexSPIONs specifically bind to EGFR-expressing tumor cells and enhance image contrast on magnetic resonance imaging. Cet-PEG-dexSPION-treated A431 cells showed significant inhibition of epidermal growth factor-induced EGFR phosphorylation and enhancement of EGFR internalization and degradation. In addition, a significant increase in apoptosis was detected in EGFR-overexpressing cell lines, A431 and 32D/EGFR, after 24 hours of incubation at 37°C with cet-PEG-dexSPIONs compared with cetuximab alone. The antibody-dependent cell-mediated cytotoxicity of cetuximab was observed in cet-PEG-dexSPIONs. The results demonstrated that cet-PEG-dexSPIONs retained the therapeutic effect of cetuximab in addition to having the ability to target and image EGFR-expressing tumors. Cet-PEG-dexSPIONs represent a promising targeted magnetic probe for early detection and treatment of EGFR-expressing tumor cells.

Keywords: epidermal growth factor receptor, cetuximab, superparamagnetic iron oxide nanoparticle, magnetic resonance imaging, sodium periodate, polyethylene glycol

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