Improving the drug delivery performance of ZIF-8 with amine functionalization as a 5-fluorouracil nanocarrier

This study investigates the effect of amine functional groups in ZIF-8 metal-organic frameworks on the loading and release of 5-fluorouracil (5-FU). The facile and cost-effective solvent-assisted linker exchange (SALE) method was used to exchange 2-methylimidazole (2-MIM) linkers with 3-amino-1,2,4-triazole (Atz) in the ZIF-8 structure, which resulted in a synthesis of ZIF-8A with 22, 53, and 74% Atz exchange, respectively. The prepared nanoparticles were characterized by 1H-NMR, XRD, FT-IR, FE-SEM, UV-Vis spectroscopy, and zeta potential analysis. Drug encapsulation efficiency results showed 12% for 5-FU@ZIF-8 which increased to 48% for 5-FU@ZIF-8A(53%). Also, the results of in-vitro experiments exhibited the pH-responsive behavior of nanocarriers and slower release for 5-FU@ZIF-8A(53%) compared to 5-FU@ZIF-8. The increase in drug encapsulation efficiency and slower release is due to the presence of the amine functional group in the structure, which improves the host-guest interactions between drug molecules and linkers. Moreover, the MTT assay was performed on MCF-7 and HFF-2 cell lines which revealed that 5-FU@ZIF-8A(53%) exhibited more significant cytotoxicity toward cancer cells while less toxicity toward normal cells compared to 5-FU@ZIF-8. These findings highlight the capability of amine-functionalized ZIF-8 as an effective drug delivery system for 5-FU and demonstrate the potential of the facial and low-cost SALE approach as a promising technique in nanocarrier development.