Nanoparticles (10) functionalized with at least one zwitterionic moiety, and compositions comprising said nanoparticles are provided. The nanoparticles (10) have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle (10) comprises a core (20), having a core surface (30) essentially free of silica, and a shell (40) attached to the core surface (30). The shell (40) comprises at least one silane- functionalized zwitterionic moiety. Further, methods of making said nanoparticles and methods of their use as diagnostic agents are provided.