An ultra-sensitive T 2-weighted MR contrast agent based on Gd3+ ion chelated Fe3O4 nanoparticles

Abstract

An ultra-sensitive T ₂-weighted MR imaging contrast agent was prepared based on Fe₃O₄ nanoparticles and Gd³⁺ ions (Fe₃O₄@Gd). Amino modified Fe₃O₄ nanoparticles were conjugated to diethylenetriamine pentaacetic acid, and finally coordinated with Gd³⁺ ions. The nanoparticles had a uniform morphology with a size of 100 nm and a Gd/Fe mass ratio of 1/110. The r ₂ (transverse relaxivity) of the Fe₃O₄ nanoparticles increased from 131.89 mM^-1 s^-1 to 202.06 mM^-1 s^-1 after coordination with Gd³⁺ ions. MR measurements showed that the aqueous dispersion of Fe₃O₄@Gd nanoparticles had an obvious concentration-dependent negative contrast enhancement. Hepatoma cells were selected to test the cytotoxicity and MR imaging effect. The application of Fe₃O₄@Gd nanoparticles as contrast agents was also exploited in vivo for T ₂-weighted MR imaging of rat livers. All the results showed the effectiveness of the nanoparticles in MR diagnosis.

Scheme 1. Schematic illustration of the formation of Fe₃O₄@Gd nanoparticles.

Fig. 1. Characterization of nanoparticles. (a) TEM image of Fe₃O₄ nanoparticles; (b) TEM image of Fe₃O₄@Gd nanoparticles; (c) EDX mapping images of one nanoparticle; (d) the magnetic hysteresis loops of Fe₃O₄ and Fe₃O₄@Gd nanoparticles at room temperature; (e) size distribution of Fe₃O₄@Gd nanoparticles; (f) zeta potential of Fe₃O₄@Gd nanoparticles; (g) IR spectra of Fe₃O₄@DTPA nanoparticles, Fe₃O₄ nanoparticles and DTPA.

Fig. 2. T ₂-weighted MR images at different Fe concentration in 0.5% agarose gel at different TE time and the analysis of relaxation rate vs. Fe concentration. (a and b) Fe₃O₄ nanoparticles. (c and d) Fe₃O₄@Gd nanoparticles.

Fig. 3. Cell viability of HepG2 cells incubated with Fe₃O₄@Gd nanoparticles at various Fe concentrations.

Fig. 4. Prussian blue staining images of HepG2 cells incubated with Fe₃O₄@Gd nanoparticles at various iron concentration ((a) – control, (b) – 10 μg mL⁻¹, (c) – 20 μg mL⁻¹, (d) – 30 μg mL⁻¹).

Fig. 5. MR investigation in vitro. (a) T₂-weighted MR images of HepG2 cells incubated with Fe₃O₄@Gd nanoparticles with iron concentration ranging from 0–30 μg mL⁻¹ and (b) the corresponding analysis of MR signal intensity.

Fig. 6. MR images of rat liver before and after vein tail injection of Fe₃O₄@Gd nanoparticles (10 mg kg⁻¹). (a) Pre-injection; (b) 30 min after injection; (c) 60 min after-injection; (d) 24 h after injection; (e) the corresponding T₂-weighted MR signal intensity of the liver.

Fig. 7. Prussian blue staining images of the major organs of SD rats ((a and b) – liver, (c) – spleen, (d) – kidney, (e) – lung and (f) – heart). The sections were acquired from rat at 24 h after intravenous injection of 10 mg kg⁻¹ Fe₃O₄@Gd nanoparticles.