A fluorescent system based on graphene quantum dots-capped magnetic hydroxyapatite-MIL-100 metal-organic frameworks for pH-sensitive and controlled release of DOX

Since metal-organic frameworks (MOFs) have shown great potential as emerging candidates in biomedical applications, it is worthwhile to construct an MOF-based drug delivery system. Hence, in this work, magnetic hydroxyapatite-MIL-100 metal-organic frameworks (SiO2@Fe3O4-HA-MIL-100) with antioxidant properties were synthesized as a novel drug delivery system through in-situ self-assembly of MIL-100 MOFs around pre synthesized magnetic hydroxyapatite nanoparticles. Then, SiO2@Fe3O4-HA-MIL-100 nanocomposites were capped with fluorescent graphene quantum dots (SiO2@Fe3O4-HA-MIL-100-GQDs) for loading and delivering of doxorubicin (DOX). The SiO2@Fe3O4-HA-MIL-100, GQDs, and SiO2@Fe3O4-HA-MIL-100-GQDs encapsulation efficiency was 80.2, 42.2, and 95.8 %, respectively. The in vitro DOX release amount after 72 h from SiO2@Fe3O4- HA-MIL-100, GQDs, and SiO2@Fe3O4-HA-MIL-100-GQDs at pH 5 was 75.8 %, 86.2 %, and 67.2 %, while at pH 7.4 was 37.3 %, 50.1 %, and 29 %, respectively. These results confirmed a pH-responsive controlled release of DOX from nanocomposites. The release mechanism of DOX from the prepared nanocomposites was also well fitted to the Korsmeyer-Peppas kinetic, Fickian diffusion, and diffusion-controlled release. In addition, the MTT assays of nanocomposites against MCF-7 breast cancer cell lines clearly illustrated that the prepared nano composites had no significant cytotoxicity, while DOX-loaded nanocomposites had notable toxicity to MCF-7 cells. The IC50 values of DOX, SiO2@Fe3O4-HA-MIL-100-DOX, GQDs-DOX, and SiO2@Fe3O4-HA-MIL-100-GQDs-DOX against MCF-7 cells calculated at about 4.2 mu g/mL, 1.8 mu g/mL, 3 mu g/mL, and 1.2 mu g/mL, respectively. The DPPH test results also showed that the nanocomposites have excellent antioxidant activity. In addition, the in vitro hemolysis results displayed neglectable hemolysis activity (lower than 5 %) of SiO2@Fe3O4-HA-MIL-100-GQDs even at a high dose. Therefore, these new drug delivery systems can be used safely as potential drug carriers in targeted cancer therapy.

Automated summary

In this study, a drug delivery system based on metal-organic frameworks was synthesized, which exhibited antioxidant properties. The results showed that the system could control the release of drugs at different pH conditions and had significant toxicity to cancer cells. Moreover, this drug delivery system had excellent antioxidant activity and low hemolysis activity.