An integrated computational and experimental study of BSA-coated MnFe2O4 nanoparticles as a drug delivery platform for quercetin

Quercetin, a bioactive flavonoid with limited bioavailability, was investigated using BSA-coated MnFe₂O₄ nanoparticles as a novel delivery system. An integrated computational and experimental approach was employed, combining DFT calculations and molecular docking simulations to analyze quercetin's interactions with the MnFe₂O₄ surface across (011), (101), and (100) facets, alongside in vitro studies to assess drug loading and release, biocompatibility, and cytotoxicity on 4T1 cells. Molecular docking showed favorable binding energies between quercetin and BSA (−5.17 kcal mol⁻¹ with Subdomain IIA), demonstrating that quercetin, even when bound to the BSA coating, retained strong interactions with the oxide surface. Reduced density gradient (RDG) analysis revealed facet-dependent adsorption mechanisms, correlating binding affinity towards Mn (through oxygen-containing functional groups) with steric interactions shown as red areas on the RDG plot. Analysis unveiled the interactions and structural features of each facet of the drug complex. Experimentally, the TEM imaging revealed the nanoparticles to possess a spherical morphology with an average diameter of around 7 nanometers and the average size of nanoparticles by DLS is 85.27 ± 0.26 nm with a PDI of 0.25. The BSA coating improved drug loading to 27.5% and resulted in a dose-dependent cytotoxic effect on 4T1 tumor cells. Specifically, a release of 62% of the loaded quercetin was observed at pH 5.7 after 120 hours, compared to only 41% at pH 7.4. The in vitro assessment also demonstrated high biocompatibility, with less than 5% hemolysis observed at concentrations up to 200 μg mL⁻¹. In vivo studies show no mouse death in the test of LD₅₀. Overall, these findings support the potential of BSA-coated MnFe₂O₄ nanoparticles as a promising drug delivery platform to enhance quercetin's stability and bioavailability for effective tumor growth inhibition.