We designed an epidermal growth factor (EGF)-containing polyamidoamine (PAMAM) Generation 4 dendrimer vector labeled with quantum dots for targeted imaging and nucleic acid delivery. 1H NMR, SDS-PAGE, and Western blotting were applied to characterize the synthesized G4.0-GGG-EGF nanoparticles. Targeting efficiency, cell viability, proliferation, and intracellular signal transduction were evaluated using HN12, NIH3T3, and NIH3T3/EGFR cells. We found that EGF-conjugated dendrimers did not stimulate growth of EGFR-expressing cells at the selected concentration. Consistent with this, minimal stimulation of post-receptor signaling pathways was observed. These nanoparticles can localize within cells that express the EGFR in a receptor-dependent manner, whereas uptake into cells lacking the receptor was low. A well characterized vimentin shRNA (shVIM) and yellow fluorescent protein (YFP) siRNA were used to test the delivery and transfection efficiency of the constructed targeted vector. Significant knockdown of expression was observed, indicating that this vector is useful for introduction of nucleic acids or drugs into cells by a receptor-targeted mechanism.