Polyvinylpyrrolidone Loaded-MnZnFe2O4 Magnetic Nanocomposites Induce Apoptosis in Cancer Cells Through Mitochondrial Damage and P53 Pathway.

MnZnFe₂O₄ ferrite was successfully synthesized using metallic chlorides and polyvinylpyrolidone, by Co-precipitate method. Deferent concentrations of PVP (0.1, 0.3, 0.5, 0.7, and 0.9) wt%, were used as capping agent to stabilize the particles and prevent them from agglomeration. The PVP content had a vital influence on enhancing the properties of the ferrite nanoparticles. From X-ray data the degree of crystallinity and the Lattice constants (a) of the nanoparticles increased from (8.92 nm) and (8.344 Å) to (19.94 nm) and (8.395 Å) respectively with increasing PVP concentrations. The morphology and average particle size of the MnZn ferrite nanoparticles were evaluated by scanning electron microscopy (SEM), the values were in a good agreement with the XRD results. Fourier transform infrared spectroscopy (FT-IR) confirmed the cubic structure with octahedral and tetrahedral, also indicated the formation of bond between PVP and surface of metallic hydroxide of ferrite nanoparticles. Vibrating sample magnetometer (VSM) analysis was performed for all samples at room temperature, results showed that the specimens exhibited a paramagnetic behavior in the absence of PVP while in the presence of PVP they have super paramagnetic characteristics. The values of saturation magnetization (Ms) (1.78–17.67 emu/g), remnant magnetization (M_r) (0.0022–0.0696 emu/g) also increased with increasing pvp concentration. Polyvinylpyrrolidone loaded-MnZnFe₂O₄ magnetic nanocomposites were used it alone or as a combination therapy with NIR laser, and alternating magnetic field (AMF) as anti-proliferative agent against breast cancer cell lines AMJ-13, MCF-7,and ovarian cancer cell line SKOV-3 as well as against normal cell line HBL. While, its capability to induce apoptosis was detected using different techniques which is acridine orange/ethidium bromide (AO/EtBr) staining and mitochondrial membrane potential (MMP), and flow cytometry assay membrane potential (MMP). q-PCR was used to investigate the changes in the expression of P53 gene. The influence of Polyvinylpyrrolidone loaded-MnZnFe₂O₄ magnetic nanocomposites in viability of breast and ovarian cancer cells alone or when they used as a combination therapy with laser photo-thermal therapy and alternating magnetic field (AMF) was also tested using MTT assay. Our results in the present study demonstrated that the inhibition activity of Polyvinylpyrrolidone loaded-MnZnFe₂O₄ magnetic nanocomposites against treated cancer cell lines increased when Polyvinylpyrrolidone loaded-MnZnFe₂O₄ nanocomposites used with NIR laser, while highly increased cytotoxic activities were observed after exposure of Polyvinylpyrrolidone loaded-MnZnFe₂O₄ nanocomposites to induction heating with AMF. Treated cancer cells with polyvinylpyrrolidone loaded-MnZnFe₂O₄ magnetic nanocomposites significantly increased ROS synthesis, with subsequent reduction of the MMP. The results of the current study show that tested compounds suppressed cancers cells' proliferation and has a growth inhibitory effect on different cancer cells, resulting in apoptosis as a novel pathway that involves mitochondrial damage mechanism via activated P53. Taken together the present data suggest that the Polyvinylpyrrolidone loaded-MnZnFe₂O₄ magnetic nanocomposites could be promising therapy protocol for cancer cells. [ABSTRACT FROM AUTHOR]