In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles

Wan Ju Hsieh, Chan Jung Liang, Jen Jie Chieh, Shu Huei Wang, I. Rue Lai, Jyh Horng Chen, Fu Hsiung Chang, Wei Kung Tseng, Shieh Yueh Yang, Chau Chung Wu, Yuh Lien Chen

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Abstract

Background: Active targeting by specific antibodies combined with nanoparticles is a promising technology for cancer imaging and detection by magnetic resonance imaging (MRI). The aim of the present study is to investigate whether the systemic delivery of antivascular endothelial growth factor antibodies conjugating to the surface of functionalized supermagnetic iron oxide nanoparticles (anti-VEGF-NPs) led to target-specific accumulation in the tumor. Methods: The VEGF expression in human colon cancer and in Balb/c mice bearing colon cancers was examined by immunohistochemistry. The distribution of these anti-VEGF-NPs particles or NPs particles were evaluated by MRI at days 1, 2, or 9 after the injection into the jugular vein of Balb/c mice bearing colon cancers. Tumor and normal tissues (liver, spleen, lung, and kidney) were collected and were examined by Prussian blue staining to determine the presence and distribution of NPs in the tissue sections. Results: VEGF is highly expressed in human and mouse colon cancer tissues. MRI showed significant changes in the T*2 signal and T2 relaxation in the anti-VEGF-NP- injected-mice, but not in mice injected with NP alone. Examination of paraffin sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice. Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.

Original languageEnglish
Pages (from-to)2833-2842
Number of pages10
JournalInternational Journal of Nanomedicine
Volume7
DOIs
Publication statusPublished - 2012

Keywords

  • Colon tumor
  • Magnetic resonance imaging
  • Nanoparticles
  • Transmission electron microscopy
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Hsieh, W. J., Liang, C. J., Chieh, J. J., Wang, S. H., Lai, I. R., Chen, J. H., Chang, F. H., Tseng, W. K., Yang, S. Y., Wu, C. C., & Chen, Y. L. (2012). In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles. International Journal of Nanomedicine, 7, 2833-2842. https://doi.org/10.2147/IJN.S32154