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Original Research

Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging

, , , , , , , , & show all
Pages 5099-5108 | Published online: 06 Oct 2016

Figures & data

Figure 1 Schematic representation of EGF1-EGFP-IONPs for glioma targeting. After being intravenously injected, the disrupted BBB and receptor-mediated endocytosis by TF-positive glioma cells and endothelial cells can provide specific retention of NPs in the tumor, resulting in MR contrast enhancement.

Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles; NPs, nanoparticles; TF, tissue factor; MR, magnetic resonance; BBB, blood-brain-barrier.

Figure 1 Schematic representation of EGF1-EGFP-IONPs for glioma targeting. After being intravenously injected, the disrupted BBB and receptor-mediated endocytosis by TF-positive glioma cells and endothelial cells can provide specific retention of NPs in the tumor, resulting in MR contrast enhancement.Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles; NPs, nanoparticles; TF, tissue factor; MR, magnetic resonance; BBB, blood-brain-barrier.

Figure 2 Characterization of NPs. TEM images of plain IONPs (A). Hydrodynamic sizes (B) and FTIR spectra (C) of NPs. T2 relaxation rate (1/T2, S−1) of plain IONPs (D), EGFP-IONPs (E) and EGF1-EGFP-IONPs (F) in aqueous dispersion. Insets show corresponding T2-weighted phantom images with different concentrations of iron.

Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles; NPs, nanoparticles; TEM, transmission electron microscopy; FTIR, Fourier transform infrared spectroscopy.

Figure 2 Characterization of NPs. TEM images of plain IONPs (A). Hydrodynamic sizes (B) and FTIR spectra (C) of NPs. T2 relaxation rate (1/T2, S−1) of plain IONPs (D), EGFP-IONPs (E) and EGF1-EGFP-IONPs (F) in aqueous dispersion. Insets show corresponding T2-weighted phantom images with different concentrations of iron.Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles; NPs, nanoparticles; TEM, transmission electron microscopy; FTIR, Fourier transform infrared spectroscopy.

Figure 3 In vitro cell viability of U87MG cells (A) and HUVECs (B) after different treatments for 24 h.

Abbreviations: HUVECs, human umbilical vein endothelial cells; EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles.

Figure 3 In vitro cell viability of U87MG cells (A) and HUVECs (B) after different treatments for 24 h.Abbreviations: HUVECs, human umbilical vein endothelial cells; EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles.

Figure 4 Targeting ability of EGF1-EGFP and EGF1-EGFP-IONPs in vitro. (A) Fluorescent images of U87MG cells and HUVECs incubated with EGF1-EGFP and EGFP. (B) Prussian blue staining of U87MG cells and HUVECs incubated with plain IONPs, EGFP-IONPs and EGF1-EGFP-IONPs. Magnification, ×400.

Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; HUVECs, human umbilical vein endothelial cells; IONPs, iron oxide nanoparticles.

Figure 4 Targeting ability of EGF1-EGFP and EGF1-EGFP-IONPs in vitro. (A) Fluorescent images of U87MG cells and HUVECs incubated with EGF1-EGFP and EGFP. (B) Prussian blue staining of U87MG cells and HUVECs incubated with plain IONPs, EGFP-IONPs and EGF1-EGFP-IONPs. Magnification, ×400.Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; HUVECs, human umbilical vein endothelial cells; IONPs, iron oxide nanoparticles.

Figure 5 Cell MRI in vitro. T2-weighted images (A) and T2 relaxation time (B) of U87MG cells and HUVECs with control, plain IONPs, EGFP-IONPs and EGF1-EGFP-IONPs treatment (from left to right).

Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; HUVECs, human umbilical vein endothelial cells; IONPs, iron oxide nanoparticles; MRI, magnetic resonance imaging; ms, milliseconds.

Figure 5 Cell MRI in vitro. T2-weighted images (A) and T2 relaxation time (B) of U87MG cells and HUVECs with control, plain IONPs, EGFP-IONPs and EGF1-EGFP-IONPs treatment (from left to right).Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; HUVECs, human umbilical vein endothelial cells; IONPs, iron oxide nanoparticles; MRI, magnetic resonance imaging; ms, milliseconds.

Figure 6 Representative in vivo T2-weighted images (A) and normalized T2 relaxation time (B, C) of mouse brain-bearing U87MG glioma before and at different time points post-injection of EGFP-IONPs (upper row, C) and EGF1-EGFP-IONPs (lower row, B).

Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles.

Figure 6 Representative in vivo T2-weighted images (A) and normalized T2 relaxation time (B, C) of mouse brain-bearing U87MG glioma before and at different time points post-injection of EGFP-IONPs (upper row, C) and EGF1-EGFP-IONPs (lower row, B).Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles.

Figure 7 Prussian blue staining of tumor and healthy brain tissues at 24 h post-injection of EGF1-EGFP-IONPs (upper row) and EGFP-IONPs (lower row). Magnification, ×200.

Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles.

Figure 7 Prussian blue staining of tumor and healthy brain tissues at 24 h post-injection of EGF1-EGFP-IONPs (upper row) and EGFP-IONPs (lower row). Magnification, ×200.Abbreviations: EGF1, epidermal growth factor-like domain-1; EGFP, enhanced green fluorescent protein; IONPs, iron oxide nanoparticles.