Efficient Endocytosis of Inorganic Nanoparticles with Zwitterionic Surface Functionalization

PEGylation, which has traditionally been the method of choice to enhance the colloidal stability of nanostructures designed for biological applications and to prevent nonspecific protein adsorption, is now being challenged by short zwitterionic ligands. Inspired by the zwitterionic nature of cell membranes, these ligands have the potential to push forward the field of nanoparticles for nanomedicine. In this work, we report a thorough analysis of the surface chemistry of silica-coated luminescent CdSe/CdS quantum dots functionalized with either PEG-silane or zwitterionic sulfobetaine-silane by quantitative nuclear magnetic resonance spectroscopy. We demonstrate the differences in the cellular uptake propensity between particles with these two ligands. Although both ligands offer good colloidal stability in a crowded cell culture medium, the zwitterionic-functionalized nanoparticles with an optimized ligand density showed to be more easily endocytosed by HeLa cells. This approach can readily be transferred to other nanoparticle systems offering a wealth of unique properties, with great potential for intracellular bioapplications.