Functionalization of MOF-5 with mono-substituents: effects on drug delivery behavior

Abstract

Metal organic frameworks (MOFs) are widely used in drug carrier research due to their tunability. The properties of MOFs can be adjusted through incorporation of mono-substituents to obtain pharmaceutical carriers with excellent properties. In this study, different functional groups of -NH₂, -CH₃, -Br, -OH and -CH₂[double bond, length as m-dash]CH are connected to MOF-5 to analyse the effect of mono-substituent incorporation on drug delivery properties. The resulting MOFs have similar structures, except for Br-MOF. The pore size of this series of MOFs ranges from 1.04 nm to 1.10 nm. Using oridonin (ORI) as a model drug, introduction of the functional groups appears to have a significant effect on the drug delivery performance of the MOFs. The IRMOFs can be ranked according to drug-loading capacity: MOF-5 > HO-MOF-5 > H₃C-MOF-5 = Br-MOF-5 > H₂N-MOF-5 > CH₂[double bond, length as m-dash]CH-MOF-5. The ORI release from ORI @IRMOFs is explored at two different pH values: 7.4 and 5.5, and the ORI@IRMOFs are ranked according to the cumulative release percentage of ORI: ORI@MOF-5 > ORI@Br-MOF-5 > ORI@H₃C-MOF-5 > ORI@H₂N-MOF-5 > CH₂[double bond, length as m-dash]CH-MOF-5 > ORI@ HO-MOF-5. In particular, the release behaviour of ORI@MOFs is described through a new model. The different drug delivery performance of MOFs may be due to the complex interactions between MOFs and ORI. In addition, the introduction of single substituents does not change the biocompatibility of MOFs. MTT in vitro experiments prove that this series of MOFs has low cytotoxicity. This study shows that the incorporation of single substituents can effectively adjust the drug delivery behaviour of MOFs, which is conducive to realization of personalized drug delivery modes. The introduction of active groups can also facilitate post-synthesis modification to achieve coupling of targeting groups. MOFs incorporated with single substituents perform favorably in terms of use as biomedical drug delivery alternative carriers in effective drug payload and flexible drug release.

Fig. 1. SEM image of ORI@MOF-5 (a), ORI@NH₂–MOF-5 (b), ORI@CH₃–MOF-5 (c), ORI@Br–MOF-5 (d), ORI@HO–MOF-5 (e) and ORI@CH₂CH–MOF-5 (f).

Fig. 2. TG and DTG diagrams of MOF-5 (a), NH₂–MOF-5 (b), CH₃–MOF-5 (c), Br–MOF-5 (d), HO–MOF-5 (e) and CH₂CH–MOF-5 (f).

Fig. 3. The drug loading capacity of MOF-5, NH₂–MOF-5, CH₃–MOF-5, Br–MOF-5, HO–MOF-5 and CH₂CH–MOF-5.

Fig. 4. SEM image of ORI@MOF-5 (a), ORI@NH₂–MOF-5 (b), ORI@CH₃–MOF-5 (c), ORI@Br–MOF-5 (d), ORI@HO–MOF-5 (e) and ORI@CH₂CH–MOF-5 (f).

Fig. 5. TG diagrams of ORI@MOF-5 (a), ORI@NH₂–MOF-5 (b), ORI@CH₃–MOF-5 (c), ORI@Br–MOF-5 (d), ORI@HO–MOF-5 (e) and ORI@CH₂CH–MOF-5 (f).

Fig. 6. (a) The release curve of ORI@MOF-5, ORI@NH₂–MOF-5, ORI@CH₃–MOF-5, ORI@Br–MOF-5, ORI@HO–MOF-5 and ORI@CH₂CH–MOF-5 under pH 5.5. (b) The total release of ORI under pH 5.5. (c) The release curve of ORI@MOF-5, ORI@NH₂–MOF-5, ORI@CH₃–MOF-5, ORI@Br–MOF-5, ORI@HO–MOF-5 and ORI@CH₂CH–MOF-5 under pH 7.4. (d) The total release of ORI under pH 7.4.

Fig. 7. Schematic illustration of release process of ORI from MOF-5s through three states.

Fig. 8. MTT assay data were presented as mean SD of viability% of three independent experiments: MOF-5 (a), NH₂–MOF-5 (b), CH₃–MOF-5 (c), Br–MOF-5 (d), HO–MOF-5 (e) and CH₂CH–MOF-5 (f).