A water-soluble molecular transporter with a dendritic core-shell nanostructure has been prepared by a tandem coordination, ring-opening, hyperbranched polymerization process. Consisting of hydrophilic hyperbranched polyglycerol shell grafted from hydrophobic dendritic polyethylene core, the transporter has a molecular weight of 951 kg/mol and a hydrodynamic diameter of 17.5 ± 0.9 nm, as determined by static and dynamic light scattering, respectively. Based on evidence from fluorescence spectroscopy, light scattering, and electron microscopy, the core-shell copolymer transports the hydrophobic guests pyrene and Nile red by a unimolecular transport mechanism. Furthermore, it was shown that the core-shell copolymer effectively transports the hydrophobic dye Nile red into living cells under extremely high and biologically relevant dilution conditions, which is in sharp contrast to a small molecule amphiphile. These results suggest potential applicability of such core-shell molecular transporters in the administration of poorly water-soluble drugs.