Abstract: Based on the mPEG-Lys-OA₂ which consisted of hydrophilic methyl-polyethylene glycol, hydrophobic oleinic acid and lysine as connecting arm, mPEG-Lys-OA₂-coated superparamagnetic iron oxide nanoparticles(PLO-SPIO NPs)were prepared by dialysis method and the mPEG-Lys-OA₂ was synthesized by our research group. Transmission electron microscopy(TEM)and dynamic light scattering(DLS)were employed respectively to characterize the morphology and size of the PLO-SPIO NPs. The concentration of iron was determined by phenanthroline spectrophotometry. The saturation magnetization was measured by vibrating sample magnetometer(VSM), and hysteresis loop was drawn. RAW264. 7 macrophages were cultured in the presence of DMSA-SPIO NPs as control and PLO-SPIO NPs. CCK-8 assay was applied to detect the cell viability. The results showed that the PLO-SPIO NPs was quasi-spherical, and that the mean hydrodynamic size and polydispersity index(PDI)were(89. 6±2. 3)nm and 0. 107, respectively. The concentration of iron was(221. 91±1. 9)μg/mL, and the superparamagnetism was conformed by the hysteresis loop with the saturation magnetization of 58. 94 emu/g. It was also found that the iron amount swallowed by the RAW264. 7 macrophages was significantly lower than the control(P< 0. 05). Consequently, the PLO-SPIO NPs prepared in this study could significantly reduce the uptake of the RES, prolong their circulation time and offer a potential promise for cancer therapy in future.