The invention provides nanostructures or products of manufacture for use as ex vivo or in vivo composition (e.g., a drug, or a therapeutic, diagnostic or imaging reagent) delivery vehicles. In one aspect, the invention provides nanoparticles comprising several compartments which in unison function as a composite nanostructure. In one embodiment, the nanoparticles of the invention comprise a combination of polymer core/lipid bilayer interface which incorporate covalently attached lipid-vascular targeting ligands. These composite nanoparticles can deliver highly effective and selective payloads for diagnostic, prophylactic or therapeutic applications.