Quan Chen,1 Siheng Li,2 Zixiong Feng,1 Meng Wang,3 Chengzhi Cai,2 Jufang Wang,3 Lijuan Zhang1 1School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 2Department of Chemistry, University of Houston, Houston, TX, USA; 3School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, People’s Republic of China Abstract: We have demonstrated a novel drug delivery system to improve the selectivity of the current chemotherapy by pH-responsive, polymeric micelle carriers. The micelle carriers were prepared by the self-assembly of copolymers containing the polybasic poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) block. The mixed copolymers exhibited a comparatively low critical micelle concentration (CMC; 1.95–5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug-loading content (24%) and entrapment efficiency (55%). Most importantly, the micelle carrier exhibited a pH-dependent conformational conversion and promoted the DOX release at the tumorous pH. Our in vitro studies demonstrated the comparable level of DOX-loaded mixed micelle delivery into tumor cells with the free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX-loaded mixed micelles were effective to inhibit the proliferation of tumor cells after prolonged incubation. Overall, the pH-responsive mixed micelle system provided desirable potential in the controlled release of anticancer therapeutics. Keywords: PDEAEMA, copolymers, pH-responsive, mixed micelle, DOX, targeting delivery