Covalent organic frameworks as precision nanocarriers for targeted drug delivery: developments, hurdles, and horizons

Covalent organic frameworks (COFs) have emerged as a versatile class of crystalline reticular materials distinguished by their high surface area, permanent porosity, and atomically precise structural tunability. Their modular synthesis enables precise control over pore size, geometry, and surface functionality, while offering excellent chemical stability and intrinsic biocompatibility. These attributes make COFs uniquely suited for applications as precision nanocarriers in targeted drug delivery. Recent advances demonstrate that COFs can encapsulate therapeutic agents with high loading efficiency and facilitate controlled, stimuli-responsive release profiles. Furthermore, the incorporation of targeting moieties through linker design or post-synthetic modification enables site-specific delivery, minimizing off-target cytotoxicity and enhancing therapeutic efficacy-particularly in oncological contexts. This review critically evaluates the current landscape of COF-based drug delivery systems, detailing structural design strategies, loading and release mechanisms, and functionalization approaches for precision targeting. We also highlight key challenges-such as scalable synthesis, pharmacokinetics, and <i>in vivo</i> stability-and outline promising research directions toward the clinical translation of COF nanocarriers for personalized medicine.