Water-Soluble Fluorinated Metal–Organic Cage based on Paramagnetic Copper as an Efficient 1H and 19F MRI Nanoprobe

Abstract

Magnetic resonance imaging (MRI) is a critical clinical diagnostic tool, but conventional 1H MRI suffers from background signal interference. 19F MRI offers a promising alternative with near-zero background noise, yet its progress depends on high-performance fluorinated probes. Existing probes often struggle to balance fluorine content, water solubility, and relaxation efficiency. To address this, we developed a structurally precise metal–organic cage (MOC) as a platform for a novel dual-modal MRI nanoprobe. Using copper ions as paramagnetic nodes and fluorinated oligoethylene glycol as ligands, we synthesized the structrally precise and water-soluble nanoprobe, MOC‑F. This nanoprobe not only significantly enhances the 1H relaxation rate through its paramagnetic copper centers, enabling high-contrast 1H MRI (r1 = 25.96 mM−1 s−1 at 298 K, 0.5 T), but also promotes an increased relaxation rate for 19F nuclei via paramagnetic relaxation enhancement (T2/T1 ratios of 0.86 at 500 MHz), thereby facilitating efficient 19F MRI. Both in vitro and in vivo studies confirmed the outstanding dual-modal imaging performance and good biocompatibility of MOC-F. This work not only presents an innovative design strategy for developing highly sensitive 19F MRI probes, but also highlights the considerable potential of MOCs in biomedical imaging, opening new avenues for the development of advanced smart MRI nanoprobes.