We designed four polymeric ligands for semiconductor quantum dots and synthesized these macromolecular constructs in four steps, starting from commercial precursors. These ligands have a poly(methacrylate) backbone with pendant thiol groups and poly(ethylene glycol) chains. The thiol groups anchor these ligands on the surface of preformed CdSe-ZnS core-shell quantum dots, and the poly(ethylene glycol) chains impose hydrophilic character on the resulting assemblies. Indeed, three of the four sets of quantum dots are soluble in aqueous environments and are stable under these conditions for days over a wide pH range (5.0-9.0). Furthermore, the polymeric coatings wrapped around the inorganic nanoparticles preserve the photophysical properties of the CdSe core and ensure relatively compact dimensions. Specifically, the luminescence quantum yield is ca. 0.4 and the hydrodynamic diameter ranges from 15 to 29 nm with the nature of the polymeric ligand. Model studies with human umbilical vein endothelial cells demonstrated that these hydrophilic quantum dots cross the cell membrane and localize either in the cytosol or in the nucleus. The length of the poly(ethylene glycol) chains appears to guide the intracellular localization of these luminescent probes. In addition, these studies indicated that these particular nanoparticles are not cytotoxic. In fact, their cellular internalization has essentially no influence on cell growth. In summary, we developed novel polymeric ligands able to impose hydrophilic character and biocompatibility on CdSe-ZnS core-shell nanoparticles. Thus, our results can lead to a new family of valuable luminescent probes for cellular imaging, based on the unique photophysical properties of semiconductor quantum dots.