The main objective of this study was to synthesize novel folic acid-functionalized diblock copolymer micelles and evaluate their solubilization of two poorly water-soluble anti-tumor drugs, tamoxifen and paclitaxel, which suffer from low water solubility and/or poor hydrolytic stability. The diblock copolymer consisted of a permanently hydrophilic block comprising 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) residues and a pH-sensitive hydrophobic block comprising 2-(diisopropylamino)ethyl methacrylate (DPA) residues. Folic acid (FA) was conjugated to the end of the MPC block so that this group was located on the micelle periphery. Tamoxifen- and paclitaxel-loaded micelles were prepared from FA-MPC-DPA copolymers prepared with two different block compositions that were designed to produce optimal solubilization of each drug. Their drug-loading capacities and aqueous stabilities were determined by high performance liquid chromatography. The hydrodynamic diameters of tamoxifen- and paclitaxel-loaded FA-MPC-DPA micelles ranged from 30 to 60 nm, as judged by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Finally, tamoxifen and paclitaxel release profiles were evaluated in phosphate buffer solution at pH 7.4 and 5. These studies demonstrated that FA-MPC-DPA micelles acted as useful drug carriers, leading to relatively slow release of both tamoxifen and paclitaxel into aqueous solution over a period of 7 days. In addition, rapid release can be triggered by lowering the solution pH to 5, which leads to protonation of the DPA block and hence rapid micellar dissociation. (c) 2006 Elsevier Ltd. All rights reserved.