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

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.