Covalent organic frameworks (COFs) are a versatile class of crystalline porous materials with growing potential in pharmaceutical and biomedical applications due to their structural precision, modular chemistry, tunable porosity, and emerging biocompatibility. Unlike prior reviews centered mainly on individual applications, this review adopts a structure-property-bioperformance-translation framework to clarify how COF design governs biological function and clinical promise. We analyze how linkage chemistry, topology, pore environment, surface properties, and particle engineering influence protein corona formation, biodistribution, degradation, therapeutic efficacy, and safety. Particular attention is given to translational challenges still under-represented in the literature, including synthesis under biomedical constraints, scalability, reproducibility, residual solvent and impurity control, sterilization, green chemistry, and regulatory compatibility. We further discuss the expanding roles of COFs in drug and biomacromolecule delivery, photodynamic, photothermal, and chemodynamic therapy, as well as in emerging immunotherapeutic and combination treatment platforms. Antimicrobial, wound-healing, diagnostic, and imaging applications are also considered, with emphasis on the relationship between framework design and functional performance. Disease-oriented case studies supported by in vivo evidence highlight both opportunities and current limitations across cancer, infectious, and cardiovascular models. This review outlines key principles for translating COFs into clinically relevant therapeutics and diagnostics.
Kolodziejczyk et al. (2026) studied this question.