pH-sensitive nanoparticles were prepared from a novel amphiphilic copolymer poly(2-phenyl-1, 3-dioxan-5-yl methacrylate-co-2-hydroxyethyl acrylate), poly(PDM-co-HEA), which was synthesized from the pH-sensitive hydrophobic monomer 2-phenyl-1, 3-dioxan-5-yl methacrylate (PDM) and the hydrophilic monomer 2-hydroxyethyl acrylate (HEA) with unit ratio (4:6) via radical polymerization. The random amphiphilic polymer could form nanoparticles in aqueous media with sizes of about 167 nm (PDI = 0.03). The morphology of the nanoparticles was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). When the nanoparticles solution was adjusted to pH = 5.5, sizes of the nanoparticles increased from 167 nm to about 800 nm within 24 h, characterized by DLS. The critical aggregation concentration (CAC) of the copolymer was determined to be 5.3 mg/L (1.7 x 10(-7) M). The insoluble Nile Red could be delivered into the Hep3B cells by the nanoparticles and released in cytoplasm determined by fluorescence microscopy. (C) 2010 Elsevier Ltd. All rights reserved.