2-deoxy-D-glucose modified supermagnetic iron oxide nanoparticles enhance the contrasting effect on MRI of human lung adenocarcinoma A549 tumor in nude mice

Abstract

To evaluate the role of 2-deoxy-D-glucose (2-DG) modified supermagnetic iron oxide nanoparticles (SPIO) (γ-Fe2O3@DMSA-DG NPs) in tumor detection as a magnetic resonance imaging (MRI) contrast agent. γ-Fe2O3@DMSA-DG NPs was prepared. The degree of A549 cells targeted absorption of γ-Fe2O3@DMSA-DG NPs was detected by Prussian blue staining, colorimetric assay, T2W and multi-echo sequence MRI. γ-Fe2O3@DMSA NPs was used as a control agent, and free D-glucose as a competitive inhibitor. Human lung adenocarcinoma A549 xenograft tumor was prepared in nude mice. Sterile aqueous suspension of γ-Fe2O3@DMSA NPs or γ-Fe2O3@DMSA-DG NPs was injected into the tail vein of nude mice. Before and 6, 12, 24, 48 h after injection, MRI imaging of the mice was performed. T2 signal intensity of the tumor, brain, liver and thigh skeletal muscles, and T2 values of the tumors were measured. The average diameter of the particles was about 10 nm, and there were no significant differences between the diameters of γ-Fe2O3@DMSA NPs and γ- Fe2O3@DMSA-DG NPs. The IR spectra showed the C-N retractable vibration peak at γ-Fe2O3@DMSA-DG NPs surface, indicating that 2-DG was conjugated to the γ-Fe2O3@DMSA NPs. The Prussian blue staining, colorimetric assay, MRI T2 signal intensity and T2 values revealed that γ-Fe2O3@DMSA-DG NPs were significantly more absorbed by A549 cells at growth peak than γ-Fe2O3@DMSA NPs, and the absorption of γ-Fe2O3@DMSA-DG NP was inhibited by free D-glucose. The results of in vivo examination showed that before and at 6, 12, 24, 48 h after injection of γ-Fe2O3@DMSA-DG NPs, the mean T2 signal intensities of the tumors were (326.00 ± 16.26)s, (276.40 ± 5.13)s, (268.40 ± 30.58)s, (240.40 ± 25.93)s, (262.20 ± 30.04)s, respectively, and the T2 values of the tumors were (735.80 ± 20.93) ms, (645.80 ± 69.58) ms, (615.00 ± 124.61) ms, (570.60 ± 67.78) ms, and (537.80 ± 105.29) ms, respectively. However, before and at 6, 12, 24, 48 h after injection of γ-Fe2O3@DMSA NPs, the mean T2 signal intensities of the tumors were (335.60 ± 4.93)s, (290.80 ± 5.93)s, (273.40 ± 15.08)s, (327.40 ± 16.65)s, and (313.20 ± 20.45)s, respectively, and T2 values were (686.00 ± 21.44)ms, (617.80 ± 69.93)ms, (645.20 ± 85.89)ms, (669.40 ± 13.72)ms, and (608.80 ± 61.90)ms, respectively. The T2 signal intensity and T2 value of the tumors were not declined generally after injection. The liver T2 signal intensity was decreased after injection of both γ-Fe2O3@DMSA-DG NPs and γ-Fe2O3@DMSA NPs, and T2 signal intensity of the brain and muscle did not show significant changes. γ-Fe2O3@DMSA-DG NPs has an ability to target glucose receptors overexpressed in tumors, and may serve as a MRI contrast agent for tumor detection.