The aim of this study is to synthesize well-defined bioreducible core crosslinked star (CCS) polymers via heterogeneous reversible addition-fragmentation transfer (RAFT) polymerization in aqueous ethanol solutions. To this end, water-soluble linear arm polymers, poly (poly (ethylene glycol) methyl ether methacrylate) (PPEGMA), poly (2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly (N,N-dimethylacrylamide) (PDMA), were prepared respectively. Next, heterogenous RAFT polymerization of the polymers with N,N'-bis(acryloyl)cystamine (BAC) as a crosslinker was systemically investigated in an aqueous ethanol solvent. It was found that these bioreducible CCS polymers with crosslinked BAC core could be prepared successfully depending on polymerization parameters. The formation of PPEGMA-based CCS polymers was affected by water volume fraction (V-w) of water-ethanol solution, reaction time, arm polymer concentration, and spacing monomer. Besides, at an optimal V-w, of 80% (i.e. the molar concentration of water is 44.44 M) and arm polymer concentration of 10% (w/v), PPEGMA-based CCS polymers at >90% yield could be achieved within 1 h. By the same V-w, and reaction time, PDMAEMA- and PDMA-based CCS polymers could also be prepared with high yield (>75%). The mechanism underlying the formation of the CCS polymers was ascribed to enhanced driving force of polymerization-induced self-assembly at an optimal V-w. These CCS polymers were degradable in thiol-containing dithiothreitol, suggesting their potential application for drug release in a reductive intracellular environment. (C) 2018 Elsevier Ltd. All rights reserved.