Synthesis and evaluation of gene delivery vectors based on PEI-modified metal-organic framework (MOF) nanoparticles

Objective(s): Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-۶۶ and NH۲-UIO-۶۶ MOFs were modified by polyethyleneimine (PEI) ۱۰۰۰۰ Da, and their efficiency for plasmid delivery was evaluated. Materials and Methods: Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A۵۴۹ cell line. Results: The sizes of DNA/nanocarriers for PEI-modified UIO-۶۶ (PEI-UIO-۶۶) were between ۲۱۲–۲۹۱ nm and ۲۶۷–۳۲۱ nm for PEI ۶-bromohexanoic acid linked UIO-۶۶ (PEI-HEX-UIO-۶۶). The zeta potential of all was positive with the ranges of +۱۶ to +۲۰ mV and +۲۳ to +۲۶ mV for PEI-UIO-۶۶ and PEI-HEX-UIO-۶۶, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI ۱۰ kDa was not significant but the PEI-HEX-UIO-۶۶ showed less cytotoxicity. Conclusion: The present study suggested that the post-synthetic modification of MOFs with PEI ۱۰۰۰۰ Da through EDC/NHS+۶-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs’ structure in order to obtain nanoparticles with better biological function in the gene delivery process.

Keywords:

Gene delivery , Metal-organic frameworks , Polyethyleneimine , Transfection , UIO-۶۶