Abstract: AimTo investigate the properties of cationic nanoparticles composed of poly (ethyleneimine)-g-poly (methyl methacrylate) (PEI-PMMA) as gene delivery carriers and explore the mechanism of PEI-PMMA nanoparticles mediated gene transfer. MethodsPEI-PMMA nanoparticles were synthesized by free radical polymerization. The morphology of nanoparticles was observed by scanning electron microscopy. The particle size and zeta potential were measured by zeta sizer. The complex between pGL3 plasmid and nanoparticles was analyzed by gel electrophoresis; and PEI-PMMA nanoparticles mediated gene transfer into HeLa cells was observed by confocal laser scanning microscopy. ResultsPEI-PMMA nanoparticles are spherical shape and monodispersity. The particle size and zeta potential are 172 nm and +50.3 mV, respectively. When pGL3 plasmid complexed with nanoparticles at N/P ratio of 5∶1 and 20∶1, the particle size of pGL3/nanoparticle complex are 133 and 139 nm and zeta potential is +21.4 and +33.7 mV, respectively. pGL3 plasmid complexed with nanoparticles completely at N/P ratio of 5∶1. PEI-PMMA nanoparticles can deliver pGL3 plasmid into HeLa cells by endocytosis and release pGL3 into the cytosol. ConclusionPEI-PMMA nanoparticles effectively transferred DNA to target cells and it is a promising non-viral carrier for gene delivery.