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

摘要

Recently, a growing interest has been seen in the development of T1–T2 dual-mode probes that can simultaneously enhance contrast on T1- and T2-weighted images. A common strategy is to integrate T1 and T2 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 αvβ3. Eu,Gd-NMOF@SiO2 nanoparticles, when intratumorally or intravenously injected, induce simultaneous signal enhancement and signal attenuation on T1-and T2-weighted images, respectively. These results suggest great potential of the NMOFs as a novel T1–T2 dual-mode contrast agent.