Targeting EGFR-overexpressed A431 cells with EGF-labeled silica-coated magnetic nanoparticles
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Human epidermal growth-factor receptor (EGFR) has emerged as an attractive target for cancer therapy. In this study, amino- or carboxyl-functionalized silica-coated maghemite nanoparticles were conjugated with epidermal growth-factor (EGF) using five different binding modes: carbodiimide chemistry, two types of homo-bifunctional cross-linking reagents, and electrostatic interactions between the nanoparticles and the EGF. The nanoparticles and their aqueous suspensions were characterized by transmission electron microscopy, zeta-potential measurements and dynamic light scattering. The binding efficiency of the EGF to the nanoparticles was measured by flow cytometry using a specific anti-EGF antibody. The ability of EGF bioconjugates to target the EGF receptors was tested using EGFR over-expressing A431 cells in comparison to EGFR negative HeLa cells. Our results showed that the bioconjugates where the EGF was bonded by carbodiimide chemistry are the most effective for the specific targeting of EGFR-expressing cells in vitro.
KeywordsBioconjugation Cellular targeting Colloidal stability Functionalization Magnetic nanoparticles
The authors are grateful for support of the Ministry of Higher Education, Science and Technology of the Republic of Slovenia within the National Research Program.
- Bachran D, Schneider S, Bachran C, Urban R, Weng A, Melzig MF, Hoffmann C, Kaufmann AM, Fuchs H (2010) Epidermal growth factor receptor expression affects the efficacy of the combined application of saponin and a targeted toxin on human cervical carcinoma cells. Int J Cancer 127:1453–1461. doi: 10.1002/ijc.25123 CrossRefGoogle Scholar
- Creixell M, Herrera AP, Ayala V, Latorre-Esteves M, Perez-Torres M, Torres-Lugo M, Rinaldi C (2010) Preparation of epidermal growth factor (EGF) conjugated iron oxide nanoparticles and their internalization into colon cancer cells. J Magn Magn Mater 322:2244–2250. doi: 10.1016/j.jmmm.2010.02.019 CrossRefGoogle Scholar
- Gabizon AA (2001) Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. Clin Cancer Res 7:223–225Google Scholar
- Meira DD, de Almeida VH, Mororó JS, Nóbrega I, Bardella L, Silva RL, Albano RM, Ferreira CG (2009) Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells. Br J Cancer 101:782–791. doi: 10.1038/sj.bjc.6605216 CrossRefGoogle Scholar
- Roberts CJ, Williams PM, Davies J, Dawkes AC, Sefton J, Edwards JC, Haymes AG, Bestwick C, Davies MC, Tendler SJB (1995) Real-space differentiation of IgG and IgM antibodies deposited on microtitre wells by scanning force microscopy. Langmuir 11:1822–1826. doi: 10.1021/la00005a063 CrossRefGoogle Scholar
- Suwa T, Ozawa S, Ueda M, Ando N, Kitajima M (1998) Magnetic resonance imaging of esophageal squamous cell carcinoma using magnetite particles coated with anti-epidermal growth factor receptor antibody. Int J Cancer 75:626–634. doi: 10.1002/(SICI)1097-0215(19980209)75:4<626:AID-IJC22>3.0.CO;2-5 CrossRefGoogle Scholar
- Taylor JM, Mitchell WM, Cohen S (1972) Epidermal growth factor. J Biol Chem 247:5928–5934Google Scholar