title: Cetuximab-conjugated iron oxide nanoparticles for cancer imaging and therapy.
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.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan ; Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Shih-Heng
authors.initials: SH
authors.lastname: Tseng
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Chou
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Chu
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D000068818:Cetuximab / Q000737:chemistry* / Q000494:pharmacology*; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D058990:Molecular Targeted Therapy / Q000379:methods; D000068936:Theranostic Nanomedicine / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003911:Dextrans; D058185:Magnetite Nanoparticles; C512478:EGFR protein, human; D066246:ErbB Receptors; C065507:ferumoxides; D000068818:Cetuximab
keywords: cetuximab; epidermal growth factor receptor; magnetic resonance imaging; polyethylene glycol; sodium periodate; superparamagnetic iron oxide nanoparticle