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 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.

Metal-organic frameworks for advanced drug delivery

“…NMOF@SiO 2 nanoparticles conjugated with a tumor-targeting peptide c (RGDyK) was prepared with a high binding affinity toward integrin αv β3 . Therefore, targeted therapy of tumor was achieved 239 .…”

Dual T1/T2 Nanoscale Coordination Polymers as Novel Contrast Agents for MRI: A Preclinical Study for Brain Tumor

“…Encouragingly, previous studies showed that biodegradable NCPs could provide T 1w properties and be combined with T 2w contrast agents to obtain nanosystems with dual-mode MRI properties. 37 Different approaches have been reported recently in order to synthesize DMCAs by Eu codoping of a Gd NCP complex, 38 the use of porphyrin ligands for the chelation of Fe, 39 or polydopaminebased coordination complex and its affinity for Fe ions. 35 Despite the progress of DMCAs, some questions remain and need to be addressed before the clinical application of DMCAs become a reality: (i) facile synthesis procedures with possibilities for scale up, (ii) chemically stable in biological environment by nontoxicity and nonaccumulation in the organism (avoiding the use of Gd and Mn ions) and (iii) high efficiency in different tissues by good biodistribution (low uptake in liver and kidneys).…”

“…Encouragingly, previous studies showed that biodegradable NCPs could provide T 1w properties and be combined with T 2w contrast agents to obtain nanosystems with dual-mode MRI properties . Different approaches have been reported recently in order to synthesize DMCAs by Eu codoping of a Gd NCP complex, the use of porphyrin ligands for the chelation of Fe, or polydopamine-based coordination complex and its affinity for Fe ions …”

Smart Metal–Organic Framework-Based Nanoplatforms for Imaging-Guided Precise Chemotherapy

“…17,21 To improve biocompatibility, the NMOFs must undergo surface modification with biopolymer (poly(ethylene glycol) 22−24 and poly(ether imide) 25 ) or SiO 2 6,26 to afford high biocompatibility. Besides the above surface camouflage, the customdesigned NMOFs should be conjugated with tumor-specific ligands, such as hyaluronic acid, 27,28 folic acid, 29−31 and arginine−glycine−aspartic acid peptide 27,32,33 to enhance the preferential accumulation of NMOFs within cancer cells.…”