Phase Transfer of Hydrophobic Nanoparticles Using a Zwitterionic Sulfobetaine Siloxane Generates Highly Biocompatible and Compact Surfaces

The renal-clearing feature of inorganic nanoparticles is highly desired for their transition to the clinic. Although high-quality ultrasmall inorganic nanoparticles can be routinely synthesized via the thermal decomposition method, rendering them suitable for in vivo application without enlarging their hydrodynamic size is still challenging. In this study, we report a facile and general method for phase transfer of hydrophobic inorganic nanoparticles from the organic phase to the aqueous phase using a zwitterionic silylation agent. The phase transfer process can be accomplished in one pot within minutes and was found to be suitable for a wide variety of inorganic nanoparticles. Interestingly, the resulting nanoparticles showed excellent colloidal stability, minimal effective hydrodynamic size, and low nonspecific affinities toward serum proteins. Thus, nanoparticles with the desired renal-clearing property were obtained. These features rendered the phase transfer method reported here considerably advantageous over previous polymer-based strategies and will be useful for preparing biocompatible nanomaterials for biomedical applications.