Metal-organic and covalent organic frameworks for precision drug delivery: a precision-by-design evidence framework for biologically accountable nanomedicine

Metal-organic frameworks and covalent organic frameworks offer a rare opportunity to design drug carriers from molecular building blocks upward. Yet high loading capacity and stimulus-responsive release alone do not constitute precision delivery.

We critically synthesized evidence on MOF and COF pore-level cargo interactions, framework and surface engineering, endogenous and externally triggered release, active targeting, biomimetic coatings, nanozyme activity and theranostic integration. Precision delivery was decomposed into five evidence-qualified dimensions: material, spatial, temporal, mechanistic and translational precision.

The evidence supports the complementary strengths of the two families across small-molecule, protein, nucleic-acid, gas and catalytic therapies. Direct evidence is strongest for individual component technologies, selected antibody-targeted systems and two-component hybrids. Recurrent evidence gaps include incomplete particle characterization in biological media, reliance on total-tissue accumulation rather than cell-specific delivery, and insufficient separation of carrier degradation from drug release.

A framework becomes precise only when it maintains a defined material identity, reaches a biologically justified compartment, releases an active payload at the intended place and time, and does so with measurable improvements in exposure, efficacy and safety. This requires a precision-by-design framework that maps claims to minimum evidence and links material critical quality attributes to biological mechanisms, translational assays and development decisions.

Abstract from PubMed Central (PMID 42948009, PMC13710936). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.