Journal of Nanoparticle Research

, Volume 13, Issue 6, pp 2285–2293 | Cite as

MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

  • Samira Rasaneh
  • Hossein Rajabi
  • Mohammad Hossein Babaei
  • Shahram Akhlaghpoor
Research Paper

Abstract

In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 ± 2.5 and 41 ± 15 nm (size range: 15–87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1–3.5. TMNs were non-toxic to the cells below the 30 μg (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

Keywords

Iron oxide nanoparticles Trastuzumab HER2 receptor MRI Contrast agent Imaging Nanomedicine 

References

  1. Agrawal A, Gutteridge E, Gee JMW, Nicholson RI, Robertson JFR (2005) Overview of tyrosine kinase inhibitors in clinical breast cancer. Endocr Relat Cancer 12:135–144CrossRefGoogle Scholar
  2. Albanell J, Codony J, Rovira A, Mellado B, Gascon P (2003) Mechanism of action of anti-HER2 monoclonal antibodies: scientific update on Trastuzumab and 2C4. Adv Exp Med Biol 532:253–268Google Scholar
  3. Artemov D, Mori N, Okollie B, Bhujwalla ZM (2003) MR molecular imaging of the HER2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Mag Res Med 49:403–408CrossRefGoogle Scholar
  4. Bange J, Zwick E, Ullrich A (2001) Molecular targets for breast cancer therapy and prevention. Nat Med 7:548–552CrossRefGoogle Scholar
  5. Bhattarai SR, Bahadur KCR, Aryal S, Bhattarai N, Kim SY, Yi HK, Hwang PH, Kim HY (2008) Hydrophobically modified chitosan/gold nanoparticles for DNA delivery. J Nanopart Res 10:151–162CrossRefGoogle Scholar
  6. Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliver Rev 56:1649–1659CrossRefGoogle Scholar
  7. Davoli A, Hocevar BA, Brown TL (2010) Progression and treatment of HER2-positive breast cancer. Cancer Chemother Pharmacol 65:611–623CrossRefGoogle Scholar
  8. Funovics MA, Kapeller B, Hoeller C, Sud HS, Kunstfeld R, Puig S, Macfeld K (2004) MR imaging of the HER2/neu and 9.2.27 tumor antigens using immunospecific contrast agents. Magn Reson Imaging 22:843–850CrossRefGoogle Scholar
  9. Hosseinkhani H, Hosseinkhani M (2009) Biodegradable polymer-metal complexes for gene and drug delivery. Curr Drug Saf 4:79–83CrossRefGoogle Scholar
  10. Hosseinkhani H, Tabata Y (2003) In vitro gene expression by cationized derivatives of an artificial protein with repeated RGD sequences, Pronectin. J Control Release 86:169–182CrossRefGoogle Scholar
  11. Hosseinkhani H, Tabata Y (2004) PEGylation enhances tumor targeting of plasmid DNA by an artificial cationized protein with repeated RGD sequences, Pronectin. J Control Release 97:157–171CrossRefGoogle Scholar
  12. Hosseinkhani H, Tabata Y (2005) Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran. J Control Release 108:540–556CrossRefGoogle Scholar
  13. Hosseinkhani H, Aoyama T, Ogawa O, Tabata Y (2003) Tumor targeting of gene expression through metal-coordinated conjugation with dextran. J Control Release 88:297–312CrossRefGoogle Scholar
  14. Hosseinkhani H, Azzam T, Tabata Y, Domb AJ (2004) Dextran–spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection. Gene Ther 11:194–203CrossRefGoogle Scholar
  15. Ito A, Shinkai M, Honda H, Kobayashi T (2005) Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng 100(1):1–11CrossRefGoogle Scholar
  16. Johnstone A, Thorpe R (1996) Immunocytochemistry, immunohistochemistry and flow cytofluorimetry. Immunochemistry in practice, 3rd edn. Blackwell Science, Berlin, pp 313–380Google Scholar
  17. Koyama Y, Barrett T, Hama Y, Ravizzini G, Choyke PL, Kobayashi H (2007) In vivo molecular imaging to diagnose and subtype tumors through receptor-targeted optically labeled monoclonal antibodies. Neoplasia 9(12):1021–1029CrossRefGoogle Scholar
  18. Kumar-Guptaa A, Guptab M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021CrossRefGoogle Scholar
  19. Lowry OH, Rosebrough NJ, Farr L, Randal RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–269Google Scholar
  20. Martin AL, Hickey JL, Ablack AL, Lewis JD, Luyt LG, Gillies ER (2009) Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells. J Nanopart Res 12(5):1599–1608CrossRefGoogle Scholar
  21. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRefGoogle Scholar
  22. Nahta R, Esteva FJ (2003) HER2-targeted therapy—lessons learned and future directions. Clin Cancer Res 9:5048–5078Google Scholar
  23. Potter M (1985) History of the BALB/c family. Curr Top Microbiol Immunol 122:1–5Google Scholar
  24. Siddiqa A, Long LM, Li L, Marciniak RA, Kazhdan I (2008) Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins Survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways. BMC Cancer 2(8):129Google Scholar
  25. Soto KF, Carrasco A, Powell TG, Garza KM, Murr LE (2005) Comparative in vitro cytotoxicity assessment of some manufactured nanoparticulate materials characterized by transmission electron microscopy. J Nanopart Res 7:145–169Google Scholar
  26. Souiri M, Mora-Ponsonnet L, Glinel K, Othmane A, Jouenne T, Duncan AC (2009) Surface assembly on biofunctional magnetic nanobeads for the study of protein-ligand interactions. Coll Surf B Biointerfaces 68:125–129Google Scholar
  27. Thorek DLJ, Chen AK, Czupryna J, Tsourkas A (2006) Superparamagnetic iron oxide nanoparticle probes for molecular imaging. Ann Biomed Eng 34(1):23–38CrossRefGoogle Scholar
  28. Yeh CH, Hsiao JK, Wang JL, Sheu F (2010) Immunological impact of magnetic nanoparticles (Ferucarbotran) on murine peritoneal macrophages. J Nanopart Res 12(10):151–160CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Samira Rasaneh
    • 1
  • Hossein Rajabi
    • 1
  • Mohammad Hossein Babaei
    • 2
  • Shahram Akhlaghpoor
    • 3
  1. 1.Department of Medical PhysicsTarbiat Modares UniversityTehranIran
  2. 2.Department of RadioisotopeNuclear Science and Technology Research InstituteTehranIran
  3. 3.Noor Medical Imaging CenterSina Hospital, Tehran Medical UniversityTehranIran

Personalised recommendations