A facile approach to synthesis of ABCDE-type H-shaped quintopolymer comprising polystyrene (PSt, C) main chain and poly(ethylene glycol) (PEG, A), poly(epsilon-caprolactone) (PCL, B), poly(L-lactide) (PLLA, D), and poly(acrylic acid) (PAA, E) side chains was described, and physicochemical properties and potential applications as drug carriers of copolymers obtained were investigated. Azide-alkyne cycloaddition reaction and hydrolysis were used to synthesize well-defined H-shaped quintopolymer. Cytotoxicity studies revealed H-shaped copolymer aggregates were nontoxic and biocompatible, and drug loading and release properties were affected by macromolecular architecture, chemical composition, and pH value. The release rate of doxorubicin from copolymer aggregates at pH 7.4 was decreased in the order PAA-b-PLLA > H-shaped copolymer > PEG-PCL-PSt star, and the release kinetics at lower pH was faster. The H-shaped copolymer aggregates have a potential as controlled delivery vehicles due to their excellent storage stability, satisfactory drug loading capacity, and pH-sensitive release rate of doxorubicin. (c) 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012