Cellular uptake of magnetite nanoparticles enhanced by NdFeB magnets in staggered arrangement

Magnetic force may greatly enhance uptake of magnetic nanoparticles (MNPs) by cultured cells; however, the effects of non-uniformity of magnetic field/ magnetic gradient on MNP internalization in culture has not been elucidated. Cellular uptake of polyacrylic acid coated-MNP by LN229 cells was measured with cylindrical NdFeB magnets arranged in a staggered pattern. The magnetic field generated by placing a magnet underneath (H-field) elicited a homogenous distribution of MNPs on the cells in culture; whereas the field without magnet underneath (L-field) resulted in MNP distribution along the edge of the wells. Cell-associated MNP (MNP_cell) appeared to be magnetic field- and concentration-dependent. In H-field, MNP_cell reached plateau within one hour of exposure to MNP with only one-min application of the magnetic force in the beginning of incubation; continuous presence of the magnet for 2 h did not further increase MNP_cell, suggesting that magnetic force-induced uptake may be primarily contributed to enhanced MNP sedimentation. Although MNP distribution was much inhomogeneous in L-field, averaged MNP_cell in the L-field may reach as high as 80% of that in H-field during 1–6 h incubation, suggesting high capacity of MNP internalization. In addition, no significant difference was observed in MNP_cell analyzed by flow cytometry with the application of H-field of staggered plate vs. filled magnet plate. Therefore, biological variation may dominate MNP internalization even under relatively uniformed magnetic field; whereas non-uniformed magnetic field may serve as a model for tumor targeting with MNPs in vivo. - Graphical abstract: Averaged MNP uptake by glioma cells in the low and non-uniformed magnetic field reached as high as 80% of that in uniformed magnetic field, which is probably due to both heterogeneous distributions of MNPs in the non-uniformed magnetic field and high capacity of the MNP uptake by these cells. - Highlights: • Enhanced sedimentation of MNPs by the magnet augments MNP uptake. • Uneven uptake of MNPs in cells between the magnets is due to nonuniformed force. • High averaged MNP uptake by cells subjected to nonuniformed force was observed. • High capacity of MNP uptake by tumor cells may hinder uniformed treatment of tumors.