Gd and Eu Co-Doped Nanoscale Metal–Organic Framework as a T1–T2 Dual-Modal Contrast Agent for Magnetic Resonance Imaging

Abstract

Recently, a growing interest has been seen in the development of <i>T</i>₁-<i>T</i>₂ dual-mode probes that can simultaneously enhance contrast on <i>T</i>₁- and <i>T</i>₂-weighted images. A common strategy is to integrate <i>T</i>₁ and <i>T</i>₂ components in a decoupled manner into a nanoscale particle. This approach, however, often requires a multi-step synthesis and delicate nanoengineering, which may potentially affect the production and wide application of the probes. We herein report the facile synthesis of a 50-nm nanoscale metal-organic framework (NMOF) comprising gadolinium (Gd³⁺) and europium (Eu³⁺) as metallic nodes. These nanoparticles can be prepared in large quantities and can be easily coated with a layer of silica. The yielded Eu,Gd-NMOF@SiO₂ nanoparticles are less toxic, highly fluorescent, and afford high longitudinal (38 mM^-1s^-1) and transversal (222 mM^-1s^-1) relaxivities on a 7 T magnet. The nanoparticles were conjugated with c(RGDyK), a tumor-targeting peptide sequence, which has a high binding affinity toward integrin α_vβ₃. Eu,Gd-NMOF@SiO₂ nanoparticles, when intratumorally or intravenously injected, induce simultaneous signal enhancement and signal attenuation on <i>T</i>₁-and <i>T</i>₂-weighted images, respectively. These results suggest great potential of the NMOFs as a novel <i>T</i>₁-<i>T</i>₂ dual-mode contrast agent.