BACKGROUND:It is vital to choose the appropriate carrier with low toxicity and high gene transfection efficiency in gene therapy, which is harmless to human body and environment. OBJECTIVE: To prepare superparamagnetic Fe3O4/SiO2-polyethyleneimine (PEI) composite particles. METHODS: Fe3O4 nanoparticles were prepared via an emulsion solvent evaporation method and superparamagnetic Fe3O4/SiO2 core shel microspheres were prepared successfuly subsequently via a modified stober method. The microspheres were further modified with PEI to obtain superparamagnetic Fe3O4/SiO2-PEI composite particles. The structures and properties of resultant composite particles microspheres were characterized by transmission electron microscopy, zeta potential and vibrating sample magnetometer. Superparamagnetic Fe3O4/SiO2-PEI composite particles were mixed with plasmid DNA at different mass ratios (29∶1, 39∶1, 49∶1, 59∶1, 68∶1, 78∶1, 88∶1). Thein vitro gene transfection ability was evaluated by Hela cels with the transfection of plasmid DNA encoded with green fluorescent protein and the transfection efficiency was determined by confocal fluorescence microscopy. RESULTS AND CONCLUSION: We successfuly synthesized the Fe3O4/SiO2-PEI composite particles with good dispersibility and even size distribution (about 100 nm). The surface charge was 21.07 mV, and the saturation magnetization was 28.05 emu/g that meant superparamagnetism. When the mass ratio was 59∶1, al the plasmid DNA was adherent to the Fe3O4/SiO2-PEI composite particles; when the mass ratio was > 59∶1, there were excessive Fe3O4/SiO2-PEI composite particles. Therefore, the mass ratio of 59:1 could lead to a better outcome for HeLa celltransfection. These results indicate that the Fe3O4/SiO2-PEI composite particles can dramaticaly improve the transfection efficiency of plasmid DNA compared with PEI.