Cyclic asparagines-glycine-arginine (cNGR) peptide was used to target gene loaded poly(lactic acid)-poly(ethylene glycol) nanoparticles (PLA-PEG NPs) to human umbilical vein endothelial cells (HUVEC). cNGR modified gene loaded PLA-PEG nanoparticles (cNGR-PLA-PEG NPs) could effectively condense DNA into small-sized complexes (< 200 nm) with positive charge (~ 10 mV) using a novel cationic surfactant, 6-lauroxyhexyl lysinate (LHLN). cNGR-PLA-PEG NPs could be internalized into HUVEC by caveolae-mediated endocytosis with higher gene transfection efficiency and lower cytotoxicity than PLA-PEG NPs.