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 nanocomposites 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 μg/mL, 1.8 μg/mL, 3 μg/mL, and 1.2 μg/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.
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