Low-frequency magnetic fields potentiate plasma-modified magneto-electric nanoparticle drug loading for anticancer activity in vitro and in vivo.

A multiferroic nanostructure of manganese ferrite barium-titanate called magneto-electric nanoparticles (MENs) was synthesized by a co-precipitation method. FTIR, Raman spectroscopy, TEM, and X-ray diffraction confirmed the presence of spinel core and perovskite shell phases with average crystallite sizes of 70-90 nm. Magnetic, optical, and magnetoelectrical properties of MENs were investigated using VSM, UV-Vis spectrophotometry, DLS, and EIS spectroscopy techniques. After pre-activation by low-pressure argon (Ar) plasma, the MENs were functionalized by a highly hydrophilic acrylic acid and Oxygen (AAc+O) mixture to produce COOH and C=O-rich surfaces. The loading and release of doxorubicin hydrochloride (DOX) on MENs were investigated using UV-vis and fluorescence spectrophotometry under alternating low-frequency magnetic fields. Plasma treatment enabled drug-loading control by changing the particles' roughness as physical adsorption and creating functional groups for chemical absorption. This led to reduced metabolic activity and cell adherences associated with elevated expression of pro-apoptotic genes (BCL-2, caspase 3) in 4T1 breast cancer cells in vitro exposed to alternating current magnetic field (ACMF) compared to MENs-DOX without field exposure. ACMF-potentiated anticancer effects of MENs were validated in vivo in tumor-bearing Balb/C mice. Altogether, our results suggest potentiated drug loading of MENs showing superior anticancer activity in vitro and in vivo when combined with ACMF.