“…Metal–organic frameworks (MOFs) have attracted enormous attention as an emerging class of porous crystalline materials composed of metallic clusters and organic ligands. Their particle size, porosity, and functionality could be purposefully designed, making them potential candidates for various applications. − In particular, for biomedical applications, it seems essential to downsize their particles to the nanometer range for efficient intracellular endocytosis. − In terms of the pore structure, inherent micropores of traditional MOFs usually restrict the mass transfer of biomacromolecules, and the utilization of active sites inside MOFs is generally not maximized, which urges the demand for the development of nanoscale hierarchically mesoporous MOFs (HMMOFs). , The controllable pore sizes and architectures of mesopores make it possible for HMMOFs to be utilized in large biomolecule-related applications, especially for the encapsulation of enzyme molecules. , Unfortunately, the nonspecific or specific interaction between HMMOFs supports and enzymes might cause the undesired conformation change of encapsulated enzymes, resulting in their activity loss. , Therefore, in order to enhance the activity of encapsulated enzymes, many attempts have been made to functionalize the skeletons of MOFs.…”