Inspired by the biosilification process, a highly benign synthesis strategy is successfully developed to synthesize PEOlated Fe3O4@SiO2 nanoparticles (PEOFSN) at room temperature and near-neutral pH. The success of such a strategy lies in the simultaneous encapsulation of Fe3O4 nanocrystals and silica precursors into the core of PEO-based polymeric micelles. The encapsulation results in the formation of a silica shell being confined to the interface between the core and corona of the Fe3O4-nanocrystal-loaded polymeric micelles. Consequently, the surface of the Fe3O4@SiO2 nanoparticle is intrinsically covered by a layer of free PEO chains, which enable the PEOFSN to be colloidally stable not only at room temperature, but also upon incubation in the presence of proteins under physiological conditions. In addition, the silica shell formation does not cause any detrimental effects to the encapsulated Fe3O4 nanocrystals with respect to their size, morphology, crystallinity, and magnetic properties, as shown by their physicochemical behavior. The PEOFSN are shown to be good candidates for magnetic resonance imaging (MRI) contrast agents as demonstrated by the high r2/r1 ratio with long-term stability under high magnetic field, as well as the lack of cytotoxicity.