Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles

Development of a multifunctional nanoparticle (NP) system allowing for dual-contrast T1- and T2-weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, superparamagnetic silica-coated iron oxide core-shell nanoparticles (Fe3O4@SiO2 NPs) with a diameter of approximately 21 nm were synthesized via a thermal decomposition approach and were aminated through silanization. The amine-functionalized Fe3O4@SiO2 NPs enabled the covalent conjugation of a paramagnetic gadolinium complex (Gd-DTPA, DTPA: diethylenetriamine pentaacetic acid) and an arginine-glycine-aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed Fe3O4@SiO2(Gd-DTPA)-RGD NPs are water-dispersible, stable, and biocompatible as confirmed by MTT cell viability assay. Relaxivity measurements show that they have a T1 relaxivity (r1) of 4.2 mm−1 s−1 and T2 relaxivity (r2) of 17.4 mm−1 s−1 at the Gd/Fe molar ratio of 0.3:1, suggesting a possibility to use them as both T1 positive and T2 negative contrast agents. In vitro and in vivo MR imaging experiments show that the developed multifunctional Fe3O4@SiO2(Gd-DTPA)-RGD NPs enable targeted dual-contrast T1- and T2-weighted MR imaging of tumor cells over-expressing high-affinity αvβ3 integrin in vitro and in vivo. Our results clearly indicate that the approach to forming multifunctional Fe3O4@SiO2(Gd-DTPA)-RGD NPs could be extended for fabricating other biologically active NPs for T1- and T2-weighted MR imaging of other biological systems with high accuracy.