Cyclic RGD‐Coated Ultrasmall Gd2O3 Nanoparticles as Tumor‐Targeting Positive Magnetic Resonance Imaging Contrast Agents

Abstract

The excellent theranostic properties of gadolinium oxide (Gd2O3) nanoparticles (GNPs) make them very useful as high‐performance positive magnetic resonance imaging (T1 MRI) contrast agents, X‐ray computed tomography (CT) contrast agents, and gadolinium neutron capture therapy (GdNCT) agents in tumor targeting. Among these applications, tumor‐targeting T1 MRI is investigated in this study. To this end, we employ cyclic RGDs (cRGDs; cyclic Arg–Gly–Asp peptides) as tumor‐targeting ligands to coat ultrasmall GNPs (particle diameter = 1.0–2.5 nm). Five types of commercial cRGDs are used in the coating. The cRGD‐coated GNPs (cRGD‐GNPs) are prepared through one‐pot syntheses. They exhibit longitudinal water‐proton relaxivity (r1) values of 10.0–18.7 s–1 mm–1, with r2/r1 ratios of 1.4–1.7 (r2 = transverse water‐proton relaxivity), which are 3–5 times higher than those of commercial Gd chelates. The in vivo tumor targeting of the cRGD‐GNPs is demonstrated by taking T1 MR images in a model mouse with a liver tumor using one of the five cRGD‐GNP sample solutions prepared. Approximately threefold contrast enhancements are observed in the T1 MR images in the tumor region of the liver than in the normal part of the liver, following intravenous administration of the solution. These results demonstrate that cRGD‐GNPs are potential tumor‐targeting T1 MRI contrast agents.