Folic acid modified superparamagnetic iron oxide nanocomposites for targeted hepatic carcinoma MR imaging

Abstract

A novel targeted MRI contrast agent for tumor cells and tumor over-expressing affinity receptor was synthesized and characterized. Dopamine (DA) was used to present functional molecules on the surface of superparamagnetic iron oxide nanoparticles (SPIONs), and dextran was conjugated with the folic acid (FA) that forms stable nanocomposites. The T2 values of the targeted and non-targeted nanoparticles at 3.0 T were 10.9 ms and 11.8 ms, respectively. The T2 relaxivity values (r2) were 91.7 s−1 mM−1 and 84.7 s−1 mM−1, respectively. The results of the competitive inhibition test suggest that the SPION-DA-dextran-FA uptake is associated with folate receptor binding. In the in vitro study, the T2 signal intensity of hepatic carcinoma cells (Bel 7402) incubated with the folate targeting nanocomposites decreased significantly. In contrast, the T2 signal did not show an obvious decrease for cells treated with the non-targeting nanocomposites. In the in vivo study, the T2 signal decreased significantly 18 hours after injection of the folate targeting contrast agent. In contrast, the maximum intensity of the non-targeting group appeared 0.5–2 hours after injection and the T2 signal intensities recovered gradually 4 hours after injection. Our results indicated that FA targeting SPIONs have the ability for use as a novel targeting MRI contrast agent and have a better targeting tropism to the Bel 7402 cells and tumor.