A water-soluble fluorinated metal-organic cage based on paramagnetic copper as an efficient ¹H and ¹⁹F MRI nanoprobe

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 issue, we developed a 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 a structurally 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 (a T₂/T₁ ratio 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.