the present invention includes compositions and methods of making an activated polymeric nanoparticle for targeted drug delivery that includes a biocompatible polymer and an amphiphilic stabilizing agent non - covalently associated with a spacer compound that includes at least one electrophile that selectively reacts with any nucleophilic on a targeting agent and places the targeting agent on the exterior surface of a biodegradable nanoparticle , wherein an active agent is encapsulated in or about the nanoparticle .