Field-controlled magnetoelectric core-shell CoFe_2O_4@BaTiO_3 nanoparticles as effective drug carriers and drug release in vitro

摘要

The targeted drug release at tumor cells while sparing normal cells is a huge challenge. Core-shell magneto electric (ME) nanoparticles have addressed this problem using shape-dependent magneto-electric attributes. The colloidally stable, core-shell cobalt ferrite@barium titanate (CFO@BTO) ME nanoparticles (NPs) used for in vitro study were synthesized using sonochemical method. The structural characteristics and core-shell morphology were analyzed by X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) respectively. Further magnetic and exchange coupling between two phases of ME nanostructures were studied at room temperature. Colloidal stability was studied in different suspension solutions (Water, SBB, PBS, and DMEM) using dynamic light scattering. Subsequently, the synthesized nanoparticles were functionalized with anticancer drugs including doxorubicin and methotrexate up to 80% via (EDC) chemistry. In vitro cytotoxicity studies carried out on human hepatocellular carcinoma (HepG2) and human malignant melanoma (HT144), cells validated the magneto-electric property of CFO@BTO nano-carriers in the presence of external magnetic field (5 mT), with significantly enhanced cytotoxicity when compared to free drugs and without field replicates. The resulted IC50 values ranging from 5.3-7.3 mu g/ml compared to 30.1-43.1 mu g/ml in the absence of a magnetic field also confirmed the involved physical attributes of magnetoelectric nanostructures. The fluorescent microscopy results also indicated the increased apoptosis in magnetic field-assisted samples. Finally, hemolysis assay indicated the suitability of CFO@BTO nano-carriers for intravenous applications at IC50 concentration.