The synthesis and gene transfection efficiency of a series of amphiphilic copolymers with poly(dimethylaminoethyl methacrylate) (PDMAEMA), and poly(propylene glycol methacrylate) (PPGMA) segments is reported. The hydrophobic PPGMA interior allows a cell-sensitizing drug such as paclitaxel to be incorporated while the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency as compared to PEI or PDMAEMA homopolymers.