Using a short-chain zwitterionic organosiloxane, silica nanoparticles were stabilized against aggregation by high ionic strength and/or proteins. Turbidimetry and dynamic light scattering showed that "zwitterated" nanoparticles did not exhibit a significant increase in hydrodynamic radius. When challenged with 3 M NaCl or 50% fetal bovine serum, aggregation was inhibited for at least 24 It, longer with mild heat treatment, which produced nanoparticles with zero net surface charge. These findings suggest "zwitteration" of silica-capped nanoparticles provides excellent stability for in vivo circulation diagnostics and therapies.