Antiepidermal growth factor receptor antibody (anti-EGFR antibody) was conjugated with the block copolymer micelle based on poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) for active targeting to EGFR overexpressing cancer cells. Doxorubicin (DOX) was encapsulated in the core of the block copolymer (MePEG-b-PCL) micelle (DOX-micelle). The mean diameters of the DOX-micelle and the anti-EGFR-PEG-b-PCL copolymer micelles loaded with DOX (DOX-anti-EGFR-micelle) were about 25 and 31 nm, respectively. The RKO human colorectal cancer cells expressing moderate degree of EGFR were incubated with free DOX, DOX-micelle, or DOX-anti-EGFR-micelle to study the distribution of DOX in the cells. When cells were incubated with free DOX, moderate degree of DOX fluorescence was observed in the nuclei. In the cells treated with DOX-micelle, the DOX fluorescence intensity in the cytoplasm was much greater than that in the nuclei. On the other hand, the nuclei of the cells treated with DOX-anti-EGFR-micelle exhibited DOX fluorescence intensity similar to that in the cytoplasm. The cytotoxicity of DOX-anti-EGFR-micelle to induce apoptosis in RKO cells was significantly greater than that of free DOX or DOX-micelle. These results demonstrated that the presence of anti-EGFR antibody on the DOX-micelle surface (DOX-anti-EGFR-micelle) increased the internalization of the DOX-micelle and nuclear accumulation of DOX, and enhanced the DOX-induced cell death. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7321-7331, 2008