title: Specific targeting of nasopharyngeal carcinoma cell line CNE1 by C225-conjugated ultrasmall superparamagnetic iron oxide particles with magnetic resonance imaging.
abstract: An accurate definition of clinical target volume (CTV) is essential for the application of radiotherapy in nasopharyngeal carcinoma (NPC) treatment. A novel epidermal growth factor receptor (EGFR)-targeting contrast agent (C225-USPIO) was designed by conjugating ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with cetuximab (C225), to non-invasively define the CTV of tumor. The immunobinding activity of C225-USPIO to NPC cell line CNE1 was confirmed by flow cytometry and immunofluorescence. The time-dependent accumulation of C225-USPIO in CNE1 cells was evaluated using Prussian blue staining. Targeted internalization and subcellular localization of C225-USPIO was confirmed by transmission electron microscope. The results indicated that C225-USPIO specifically bound to EGFR on the surface of CNE1 cells and was taken up into the cell. The uptake of C225-USPIO by CNE1 cells increased significantly with time, when compared with human IgG-USPIO. In addition, 4.7 T magnetic resonance imaging (MRI) revealed that C225-USPIO had a capacity to accumulate in the CNE1 cells, with a resultant marked decrease in MRI T2-weighted signal intensity over time. These findings imply that C225-USPIO has the potential as an MRI contrast agent and can be employed to non-invasively detect early-stage NPC with EGFR overexpression. This provides sufficient theoretical basis for commencing in vivo experiments with the compound.
authors.affiliation: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Liu
authors.forename: Chunli
authors.initials: C
authors.lastname: Chen
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Hu
authors.forename: Qi
authors.initials: Q
authors.lastname: Mei
authors.forename: Hong
authors.initials: H
authors.lastname: Qiu
authors.forename: Guoxian
authors.initials: G
authors.lastname: Long
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry / Q000648:ultrastructure; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; C000499:ferric oxide; D066246:ErbB Receptors; D000068818:Cetuximab