Safety, In Vivo Fate, and Degradation of MOF Nanomedicines: Toward Translational Evaluation

Metal-organic frameworks (MOFs) are porous hybrid nanomaterials assembled from metal ions or clusters and organic ligands. Owing to their tunable structures, versatile compositions, and exceptional payload capacities, MOF-based systems have attracted increasing interest in drug delivery and theranostics. Yet, despite rapid progress in efficacy-focused studies, translational evaluation remains limited by incomplete evidence on safety, in vivo fate (pharmacokinetics), and degradation. This review examines MOF nanomedicines through a three-element evidence-chain framework and a four-level material evaluation and substantiation (MES) grading system to relate commonly reported endpoints to development-relevant questions. Major degradation patterns across representative MOF families are summarized, and the influence of surface engineering on safety, in vivo fate, and degradation is discussed. Representative studies are re-examined to illustrate how evidence gaps in these dimensions may affect translational interpretation. Key priorities for the field include dose standardization, quantitative in vivo evaluation, harmonized degradation assays, long-term and repeat-dose studies, and more consistent formulation reporting. By integrating these issues into a unified evidence-chain framework, this review aims to support a more comparable, interpretable, and development-relevant evaluation of MOF nanomedicine research.