The in vivo delivery of nucleic acids is targeted by delivery of the nucleic acid in a complex with cross-linked nanoparticles; where the nanoparticles comprise cross-linked neutral amphipathic molecules, cationic amphipathic molecules and targeting amphipathic molecules. Optionally the cationic and targeting amphipathic molecules are also cross-linked. A targeting moiety present on the targeting amphipathic molecule provides for selective delivery of the complex to a predetermined target site, e.g. blood vessels, endothelial cells, tumor cells, liver cells, and the like.