Nanospheres, consisting of a Fe 3 O 4 core, a silica inner shell and dendritic poly(ester amine) (PEA) outer shell, were synthesized via the sol-gel reaction, and successive Michael addition and alkyne-azide click chemistry. The resultant PEA dendrimer-grafted magnetic nanoparticles (Fe 3 O 4 -g-PEA) were characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, and thermogravimetric (TGA) analysis. Transmission electron microscopy (TEM) images reveal that the Fe 3 O 4 -g-PEA magnetic nanoparticles (MNPs) have a uniform size distribution of about 30 nm in diameter. The hydrodynamic size of Fe 3 O 4 -g-PEA MNPs changes reversibly with pH of the aqueous medium in the pH range of 3 to 9. The clickable alkyne groups on the surface of Fe 3 O 4 -g-PEA MNPs endow these nanoparticles with a functionalizable surface via alkyne-azide click chemistry. Assays with 3T3 fibroblasts and RAW macrophage cells indicate that the Fe 3 O 4 -g-PEA MNPs possess very low cytotoxicity. Hence, the PEA dendrimer-grafted magnetic nanospheres have potential applications as biomedical materials.