Surface engineered metal-organic frameworks as active targeting nanomedicines for mono- and multi-therapy

The precision tenability of metal-organic frameworks (MOFs) enables the efficient encapsulation of a wide variety of small-molecule pharmaceuticals and macromolecular cargos, such as nucleic acids and proteins. MOFs, assembling of organic ligands and metal ions/metal clusters via coordinative bonds, offer advanced features in medicine and drug delivery due to their ultrahigh porosity, diverse functional groups, and versatile structures. After surface modification with active targeting moieties, MOFs can specifically transfer a high amount of payload to the site of action due to the high internal surface area. This review summarizes the unique properties of MOFs and their advantages as nanocarriers for drug targeting to treat different diseases. At first, we reviewed the structures of MOFs, and the corresponding synthesis approaches and characterization techniques. Then, the state-of-the-art strategies to functionalize MOFs with targeting moieties are discussed. Regarding the most recent active targeting delivery applications of MOFs, critical issues to fabricate an efficient carrier that can bind to overexpressed cell-surface receptors are discussed. Moreover, MOF-based nanocarriers are categorized based on the ligands (i.e., proteins, peptides, aptamers, small molecules, and polysaccharides) used to deliver therapeutic agents through active targeting. Finally, challenges and prospects are highlighted to provide context for future usage of MOFs as efficient drug delivery systems.