Size-dependent transfection efficiency of PEI-coated gold nanoparticles

Gold nanoparticles (Au NPs) are promising vectors for gene delivery applications. In order to gain insight on the influence of particle size on cell transfection, Au NPs were combined with poly(ethylenimine) (PEI) to prepare two sets of PEI-coated Au NPs having particle-size distributions centered at about 6 nm (<10 nm Au-PEI NPs) or 70 nm (<100 nm Au-PEI NPs), respectively. Au-PEI NPs were coupled to a variety of plasmids carrying reporter or suicide genes to prepare Au-PEI NPs/DNA complexes, and human osteosarcoma Saos-2 cells were used to investigate the performance of the Au-PEI NPs as transfection vectors in serum-containing media. The conjugates of DNA with both types of Au-PEI NPs were found to be negatively charged. In spite of the electrostatic repulsion that occurs between the surface of the cell and the surface of the plasmid-conjugated NPs, cell internalization was observed for both kinds of Au-PEI NPs. Cells were efficiently transfected with complexes derived from <10 nm Au-PEI NPs, but not with the <100 nm Au-PEI NPs. Large aggregates of NPs associated with DNA were found in endocytic vesicles of cells incubated with <100 nm Au-PEI NPs, while the success of the smaller Au-PEI NPs as transfection vectors was related to their lower agglomeration state inside cells and to endosomal escape of DNA.