Synthesis, Characterization, and Toxicity Evaluation of Size-Dependent Iron-Based Metal-Organic Frameworks

Iron-based metal-organic frameworks (Fe-MOFs) are promising for biomedical and environmental applications due to their porosity, tunable chemistry, and biocompatibility. This study examines how particle size, morphology, and ligand composition affect the properties and cytotoxicity of MIL-101(Fe) and MIL-88A. MIL-101(Fe) (octahedral) and MIL-88A (rod-like) were synthesized with a controlled size (~200 nm to ~5 μm). Both showed a high crystallinity and stability. Cytotoxicity assays in A549 cells revealed size- and structure-dependent effects: smaller particles of MIL-88A caused greater toxicity (32.5% viability) than MIL-101(Fe) (66.1% viability at 100 μg/mL), while larger particles were less toxic. MIL-88A also induced higher reactive oxidative species (ROS) levels and degraded more rapidly, releasing more Fe ions. Toxicity predication analysis indicated the higher inherent toxicity of MIL-88A's ligand (fumaric acid) compared to MIL-101(Fe)'s terephthalic acid. These results demonstrate that structural and chemical factors collectively influence Fe-MOFs' biocompatibility and highlight the importance of rational design for safer MOF applications.