Metal-organic frameworks (MOFs) provide diverse applications across a wide range of scientific disciplines, including drug/nucleic acid (NA) delivery. In the subclass of MOFs, zeolitic imidazolate framework-8 (ZIF-8) is well regarded due to its exceptional physicochemical properties. Biomolecules can be encapsulated and released under precise conditions within ZIF, making it an important material for materials science and biomedical applications. Different solvents and synthesis methods influence the ZIF's topologies and framework structures. The physicochemical properties of plasmid-encapsulated ZIF (plasmid@ZIF) can be controlled by tuning the precursors and biomolecular concentration. Using plasmid@ZIF, this study demonstrated that nucleic acids can be loaded precisely and released with a controlled bioactivity within cells. It was found that the ZIF phases substantially influenced both NA delivery into the cell and physicochemical properties. As a result of this study, we better understand MOFs' potential in NA delivery, and it emphasizes the importance of precisely controlling their physicochemical properties.
Keywords: MOF; ZIF; biocompatibility; crystal phase; gene delivery; nucleic acid.