Advances in surface-modified nanometal-organic frameworks for drug delivery

Nanometal-organic frameworks (NMOFs) are porous network structures composed of metal ions or metal clusters through self-assembly. NMOFs have been considered as a promising nano-drug delivery system due to their unique properties such as pore and flexible structures, large specific surface areas, surface modifiability, nontoxic and degradable properties. However, NMOFs face a series complex environment during in vivo delivery. Therefore, surface functionalization of NMOFs is vital to ensure that the structure of NMOFs remain stable during delivery, and can overcome physiological barriers to deliver drugs more accurately to specific sites, and achieve controllable release. In this review, the first part summarizes the physiological barriers that NMOFs faced during drug delivery after intravenous injection and oral administration. The second part summarizes the current main ways to load drugs into NMOFs, mainly including pore adsorption, surface attachment, formation of covalent/ coordination bonds between drug molecules and NMOFs, and in situ encapsulation. The third part is the main review part of this paper, which summarizes the surface modification methods of NMOFs used in recent years to overcome the physiological barriers and achieve effective drug delivery and disease therapy, which are mainly divided into physical modifications and chemical modifications. Finally, the full text is summarized and prospected, with the hope to provide ideas for the future development of NMOFs as drug delivery.