ObjectiveTo synthesize P123ylated polyamidoamine (PAMAM) copolymers and to evaluate the feasibility of using the copolymers as gene delivery agent. MethodsPluronic P123 modified PAMMA copolymers were synthesized and characterized. The cytotoxicity of the dendrimers was evaluated by the MTT assay using A375, 293T and HepG2 cells. The transfection efficiency of the complexes formed by plasmid with P123ylated PAMAM was evaluated using HepG2 cells. ResultsThe P123ylated PAMAM copolymers had a high purity; the particle sizes and zeta potentials of the complexes were suitable for gene delivery. P123ylated PAMAM could decrease cytotoxicity and increase in vitro transfection efficiency. ConclusionP123ylated PAMAM is a new copolymers agent suitable for gene delivery.