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

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 T 2 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.

Vascular targeting of nanoparticles for molecular imaging of diseased endothelium

“…Optimal MR imaging with SPIO particles depends on their magnetic properties, which, as studies have shown, depend on particle size and shape [181], [182]. SPIO particles functionalized with integrin targets [183] and VEGFR [184] have been used for molecular MR imaging of the tumor-associated endothelium. By further engineering of SPIO particles to form a chain, recent studies have shown targeting to tumor vascular integrins resulted in increased detection of breast tumor metastasis using MRI [85].…”

Colorectal Cancer from Molecular Pathways to Gene Therapy

“…(Table 1) Table 1. Gene therapy formulations with eluting drugs -Magneto-fluorescent silica nanoparticles (MFSN) [70] -Folic acid conjugated guar gum nanoparticles (MTXFA-GGNP) -Wheat germ agglutinin (WGA)-functionalised chitosan-Ca-alginate (CTS-Ca-ALG) microparticles (MPs) [71] -Anti-VEGF antibodyconjugated dextran-coated iron oxide nanoparticles (anti-EGF-NPs) [72] -HA modified mesoporous silica nanoparticles (HA-MSNs) [73] Discussion Current screening methodology is efficient, however; a novel approach regarding therapy is needed. Several efforts have been made towards identifying the genome of CRC cancer and therefore providing targeted therapy, mostly in the form of chemotherapy or inhibitors.…”

Novel delivery approaches for cancer therapeutics

“…Active targeting resulted in higher accumulation in cancer cells with significantly improved contrast MR imaging [240]. Targeting ligands conjugated to MNP was exploited for theranostics purposes ranging from small molecule nutrient transporters such folate [241–243] to macromolecules like Trastuzumab [244–246], single-chain anti-epidermal growth factor antibody [247], anti-epidermal growth factor receptor antibody [248], anti-vascular endothelial growth factor antibody (VEGF) [249, 250] and aptamers [251], [252]. A number of small molecular weight peptide have also been investigated including arginylglycylaspartic acid (RGD) [243, 253], bombesin [254, 255], and luteinizing hormone releasing hormone [256, 257]; highly cationic peptides like CPP [258], myristoylated poly-arginine peptide (MPAP) [259, 260] and HIV-TAT [261].…”