Disulfide-centered star-shaped poly(epsilon-benzyloxycarbonyl-l-lysine)-b-poly(ethylene oxide) block copolymers (i.e., A2B4 type Cy-PZlys-b-PEO) were synthesized by the combination of ring-opening polymerization and thiol-yne chemistry. Their molecular structures and physical properties were characterized in detail by FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, wide-angle X-ray diffraction, and polarized optical microscope. Despite mainly exhibiting an -helix conformation, the inner PZlys blocks within copolymers greatly prohibited the crystallinity of the outer PEO blocks and presented a liquid crystal phase transition behavior in solid state. These block copolymers Cy-PZlys-b-PEO self-assembled into nearly spherical micelles in aqueous solution, which had a hydrophobic disulfide-centered PZlys core surrounded by a hydrophilic PEO corona. As monitored by means of DLS and TEM, these micelles were progressively reduced to smaller micelles in 10 mM 1,4-dithiothreitol at 37 degrees C and finally became ones with a half size, demonstrating a reduction-sensitivity. Despite a good drug-loading property, the DOX-loaded micelles of Cy-PZlys-b-PEO exhibited a reduction-triggered drug release profile with an improved burst-release behavior compared with the linear counterpart. Importantly, this work provides a versatile strategy for the synthesis of the disulfide-centered star-shaped polypeptide block copolymers potential for intracellular glutathione-triggered drug delivery systems. (c) 2014 Wiley Periodicals, Inc.