Metal-organic frameworks (MOFs) entered biomedicine through a simple idea: their permanent porosity made them attractive materials for cargo loading, protection, and release. This perspective argues that, with few exceptions, biomedical MOFs are not biologically inert carriers and should not be developed as though they were. In biological environments, they behave instead as metastable, structurally dynamic, programmable coordination materials whose composition, particle structure, and environmental transformation directly shape biological outcomes. This case is developed through three interconnected themes: coordinated disassembly and transient protection; nonideal particulate transport shaped by size, morphology, and defects; and framework-derived biological activity arising from metals, ligands, and degradation products. Together, these features show why MOF performance in biology is poorly described by surface area, pore volume, and loading capacity alone. The more productive direction is therefore not to ignore or suppress framework bioactivity, but to work with it deliberately, treating the framework itself as part of the mechanism by which a biomedical MOF functions. Viewed this way, the future of the field lies less in approximating passive delivery systems and more in engineering dynamic materials whose disassembly, trafficking, and compositional bioactivity can be used to shape biological responses.
Jeremiah J. Gassensmith (Wed,) studied this question.