Polymthyl methacrylate-based stealth and functional nanospheres, specifically designed for the reversible adsorption of oligonucleotides (ODN), were prepared by emulsion polymerization of methyl methacrylate in the presence of an ionic comonomer, namely a quaternary ammonium salt of 2-(dimethylamino)ethyl methacrylate, and a nonionic comonomer, namely a poly(ethylene glycol) methacrylate. The nanosphere size is substantially affected by the amount of both the nonionic and ionic comonomers. By appropriately adjusting the concentrations of the ionic and nonionic comonomers, the quaternary ammonium group and PEG chain surface densities can be finely tuned. Accordingly, a great variety of core-shell-type nanospheres, able to bind ODN and to induce dysopsonic effect, can be obtained.