This work focuses on the synthesis and self-assembly of biodegradable and anionic double hydrophilic diblock copolymers (DHBCs) poly(ethylethylene phosphate)-block-poly[2-(succinyloxy)ethyl methacrylate] (PEEP-b-PSEMA) with different molecular weights and compositions, which were prepared via a combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and polymer reaction. The chemical structures of these well-defined diblock copolymers were confirmed by H-1 NMR and FT-IR analyses. GPC results indicated that the copolymers showed symmetric peak and relatively narrow polydispersities. Subsequently, pH-responsive micellization behaviors of PEEP-b-PSEMA diblock copolymers were investigated by fluorescence probe method, dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. The results demonstrated that these diblock copolymers were able to self-assemble into micelles with various sizes depending on the variation of pH values. Naproxen (NAP), a poorly water-soluble drug, was selected as the model drug and encapsulated into the core of micelles via dialysis method. The in vitro release behavior of NAP from these micelles was pH-dependent and could be accelerated in the presence of phosphodiesterase I which could promote the degradation of polyphosphoesters. Cytotoxicity tests by MTT assay showed that these block copolymers possessed favorable biocompatibility against HeLa cells, revealing that this kind of biodegradable, biocompatible and pH-responsive block copolymer would be served as a promising material for drug delivery. (C) 2012 Elsevier Ltd. All rights reserved.