This study presents a targeted and stimuli-responsive drug delivery system to increase the therapeutic window of chemotherapeutic agents. Galactose was expressed on an amphiphilic, temperature- and pH-sensitive copolymer of N-isopropylacrylamide, N,N-dimethylacrylamide and 10-undecenoic acid. The polymer would self-assemble in aqueous medium, and was used to encapsulate paclitaxel. Various synthesis parameters were examined to achieve polymers that provide high drug loading and rapid release in a temperature- and pH-responsive manner. In the target hepatocyte cell line, the stimuli-responsive, galactose-expressing particles were significantly more toxic than the non-stimuli-responsive particles as well as the non-targeted particles. (C) 2010 Elsevier Ltd. All rights reserved.