Chelating ligand-bridged IO-Gd nanoparticles with enhanced contrast performance for dual-mode MRI

Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique that has been widely applied in the clinical diagnosis of diseases across various fields. Currently, there is a dearth of high-performance dual-mode contrast agents that provide precise diagnostic information for complex diseases. In this study, iron oxide-gadolinium nanoparticles (IO-Gd NPs) bridged by hydrophilic ligand ethylenediamine tetramethylenephosphonic acid (EDTMP) are designed inspired by Solomon-Bloembergen–Morgan (SBM) theory, where T₁ and T₂ relaxivity increase with a reduction in Gd content. In particular, the NPs with minimum Gd content exhibit excellent dual-mode contrast performance (r₁ = 94.42 mM⁻¹ s⁻¹, r₂ = 343.62 mM⁻¹ s⁻¹). The underlying mechanism is that the bridged EDTMP coordinate limits Gd tumbling and forces Gd³⁺ to expose itself to the surface of the NPs. This provides more opportunities for water molecules to coordinate with Gd³⁺ and significantly enhances proton relaxivity. Moreover, the hydrophilicity of the ligand enhances the water dispersion stability of the NPs and increases the exchange rate of water protons near the NPs, further enhancing the dual-mode contrast effect. Finally, the biocompatibility and in vitro/vivo imaging performances of the IO@EDTMP-Gd NPs are systematically evaluated, and the results demonstrate their potential as dual-mode contrast agents. This study provides a new strategy for developing dual-mode MRI contrast agents that can further improve the accuracy of MRI in the diagnosis of complex diseases.