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.