Topology-dependent <i>T</i> ₂ relaxivity in Fe ₃ O cluster-based MOFs for enhanced tumor monitoring <i>via</i> MRI

Metal-organic frameworks (MOFs) are crystalline porous materials with tunable structures, where metal ions or clusters serve as magnetic centers and organic ligands offer spatial separation. These characteristics, combined with their diverse topologies, make MOFs promising candidates for contrast agents (CAs) in magnetic resonance imaging (MRI). Herein we synthesized four MOFs based on the same triangular Fe₃O clusters with different topologies: MIL-101(Fe) (moo net), MIL-100(Fe) (mtn net), MIL-59(Fe) (pcu net), and MIL-88B(Fe) (acs net). To clarify the relationship between topologies and <i>T</i>₂ relaxivities, the MOFs were tailored into uniform, nanoscale spherical morphologies. Notably, the value of <i>T</i>₂ relaxivity for MIL-88B(Fe) with acs topology is nearly three times that for MIL-101(Fe) with moo topology at 7.0 T. By comparing the magnetic properties of Fe₃O molecular clusters and Ga-doped MIL-88B(Fe), our analysis demonstrated the significant advantage of MOFs with fixed arrays, adjustable components and diverse topologies in enhancing magnetic relaxation. Cellular MRI experiments further revealed that MIL-88B(Fe) could differentiate between M1 and M2 macrophages, highlighting its potential for monitoring tumor progression. These findings offer valuable insights into how MOF topology can be strategically utilized to enhance <i>T</i>₂ relaxivities for MRI applications.