In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles
Journal
International Journal of Nanomedicine
Journal Volume
7
Pages
2833 - 2842
Date Issued
2012
Author(s)
Hsieh W.-J.
Liang C.-J.
Chieh J.-J.
Tseng W.-K.
Yang S.-Y.
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. ? 2012 Hsieh et al, publisher and licensee Dove Medical Press Ltd.
SDGs
Other Subjects
antineoplastic agent; biological marker; dextran; ferric ferrocyanide; ultrasmall superparamagnetic iron oxide; unclassified drug; vascular endothelial growth factor antibody iron oxide nanoparticle conjugate; animal cell; animal experiment; animal tissue; article; cellular distribution; colon cancer; controlled study; disease marker; drug distribution; drug uptake; female; histopathology; immunocytochemistry; immunohistochemistry; immunoreactivity; in vitro study; in vivo study; male; material coating; molecular imaging; mouse; nonhuman; nuclear magnetic resonance imaging; particle size; protein determination; protein expression; protein localization; reaction time; tissue distribution; transmission electron microscopy; upregulation; Western blotting; Animals; Antibodies; Antineoplastic Agents; Cell Line, Tumor; Colonic Neoplasms; Dextrans; Female; Humans; Immunohistochemistry; Immunotoxins; Liver; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Spleen; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays; Mus
Type
journal article