Confining metal nanoparticles and nanoclusters in covalent organic frameworks for biosensing and biomedicine

Metal nanoscale particles, primarily including metal nanoparticles (MNPs) and nanoclusters (MNCs), have garnered substantial interests owing to their unique electronic configurations and distinct physicochemical properties. However, practical applications are frequently constrained by their limited stability and aggregation tendency. Covalent organic frameworks (COFs), featuring highly ordered periodic architectures, have emerged as ideal porous matrices for hosting metal nanoparticles. The resulting metal-embedded COFs synthesized through adsorption methods (M/COFs) or in-situ reduction (M@COFs) not only mitigate nanoparticle aggregation and enhance stability but also demonstrate synergistic effects that generate enhanced or novel functionalities, significantly broadening their application potential. This review firstly examines adsorption-based synthesis strategies for M/COFs through physical and chemical approaches. Subsequently, we analyze in-situ reduction methods for M@COFs, categorizing them by reduction pathways: deposition, impregnation-pyrolysis, and “one-step” synthesis. Special attention is given to an emerging pore wall engineering strategy within in-situ reduction approach. The biosensing and biomedical applications of metal-embedded COFs are systematically examined, highlighting their comparative advantages over conventional nanomaterials in sensing and antimicrobial applications. While metal-embedded COFs remain in their developmental infancy and face considerable challenges, the controlled synthesis of multifunctional variants promises transformative potential across biomedical domains.