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

Abstract

The excellent theranostic properties of gadolinium oxide (Gd 2 O 3 ) nanoparticles (GNPs) make them very useful as high‐performance positive magnetic resonance imaging ( T 1 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 T 1 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 ( r 1 ) values of 10.0–18.7 s –1 m m –1 , with r 2 / r 1 ratios of 1.4–1.7 ( r 2 = 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 T 1 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 T 1 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 T 1 MRI contrast agents.