Amino Acid-Coated Zeolitic Imidazolate Framework for Delivery of Genetic Material in Prostate Cancer Cell

Abstract

Metal–organic frameworks (MOFs) are currently under progressive development as a tool for non-viral biomolecule delivery. Biomolecules such as proteins, lipids, carbohydrates, and nucleic acids can be encapsulated in MOFs for therapeutic purposes. The favorable physicochemical properties of MOFs make them an attractive choice for delivering a wide range of biomolecules including nucleic acids. Herein, a green fluorescence protein (GFP)-expressing plasmid DNA (pDNA) is used as a representative of a biomolecule to encapsulate within a Zn-based metal–organic framework (MOF) called a zeolitic imidazolate framework (ZIF). The synthesized biocomposites are coated with positively charged amino acids (AA) to understand the effect of surface functionalization on the delivery of pDNA to prostate cancer (PC-3) cells. FTIR and zeta potential confirm the successful preparation of positively charged amino acid-functionalized derivatives of pDNA@ZIF (i.e., pDNA@ZIFAA). Moreover, XRD and SEM data show that the functionalized derivates retain the pristine crystallinity and morphology of pDNA@ZIF. The coated biocomposites provide enhanced uptake of genetic material by PC-3 human prostate cancer cells. The AA-modulated fine-tuning of the surface charge of biocomposites results in better interaction with the cell membrane and enhances cellular uptake. These results suggest that pDNA@ZIFAA can be a promising alternative tool for non-viral gene delivery.

Impact of nucleic acid encapsulated MOF crystal phase on protein corona formation

“…ZIF-based MOFs have been extensively investigated for delivering therapeutic proteins and nucleic acids. 6–8,31 These studies have mainly focused on maximising the loading of biomolecules in MOFs and their release on demand. The formation of protein corona around biomolecule-encapsulated ZIFs has not yet been investigated.…”