Abstract
PURPOSE: This study aims to evaluate the effect of dimercaptosuccinic acid (DMSA)-coated superparamagnetic iron oxide (γ-Fe(2)O(3)@DMSA) bearing the 2-deoxy-D-glucose (2-DG) ligand on targeting tumors with high-glucose metabolism. PROCEDURES: γ-Fe(2)O(3)@DMSA and 2-DG-conjugated γ-Fe(2)O(3)@DMSA (γ-Fe(2)O(3)@DMSA-DG) were prepared. The glucose consumption of MDA-MB-231 and MCF-7 breast cancer cells and human mammary epithelial cells (HMEpiCs) was assessed. Cells were incubated with γ-Fe(2)O(3)@DMSA or γ-Fe(2)O(3)@DMSA-DG, and MDA-MB-231 cells which exhibited the highest glucose consumption were used in breast cancer xenografts. Tumor targeting was studied by magnetic resonance imaging and Prussian blue staining in vivo. RESULTS: Glucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of γ-Fe(2)O(3)@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of γ-Fe(2)O(3)@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of γ-Fe(2)O(3)@DMSA in either cell line. In vivo, γ-Fe(2)O(3)@DMSA-DG could be detected in the liver and in tumors post-injection, while γ-Fe(2)O(3)@DMSA was nearly undetectable in tumors. CONCLUSIONS: 2-DG-coated γ-Fe(2)O(3)@DMSA improved tumor targeting of γ-Fe(2)O(3)@DMSA which can be assessed by magnetic resonance imaging.