pH-dependent temperature- sensitive poly(ε-caprolactone)-graft-poly(2-(dimethylamino) ethyl methacrylate) (PCL-g-PDMAEMA), a kind of degradable, amphiphilic, cationic copolymer, was synthesized. PCL-g-PDMAEMA was self-assembled into core-shell nanoparticles with an ultralow critical association concentration at about 8.1 × 10−4 g L−1. It was found that PCL-g-PDMAEMA nanoparticles were able to simultaneously entrap hydrophobic paclitaxel and load DNA. Hydrophobic drug paclitaxel, loaded by PCL-g-PDMAEMA NPs, could be released faster in an acidic environment than in a neutral environment, and PCL-g-PDMAEMA NPs showed a comparable in vitro gene transfection efficiency to Lipofectamine 2000. In addition, the gene transfection efficiency was enhanced by the addition of 5% serum. Besides, confocal microscopic measurements indicated that PCL-g-PDMAEMA nanoparticles/DNA polyplexes could escape from the endosome and release the payloads effectively in cytoplasm. These results suggest PCL-g-PDMAEMA has great potential for achieving the synergistic effect of drug and gene therapies in vivo.
