[2-deoxy-D-glucose modified supermagnetic iron oxide nanoparticles enhance the contrasting effect on MRI of human lung adenocarcinoma A549 tumor in nude mice].
摘要
OBJECTIVE: 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. METHODS: 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. RESULTS: 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-Fe