Six-armed biodegradable star polymers made from polystyrene (polySt), poly(polyethylene glycol) acrylate (polyPEG-A) and the block copolymer, polySt-b-polyPEG-A were synthesized using a 'core-first' methodology via RAFT polymerization. Disulfide linkages between the core and the arms conferred biodegradability on the stars. The star architectures were found to degrade rapidly on treatment with DL-dithiothreitol (DTT) and degrade more slowly in the presence of glutathione (GSH), the most abundant intracellular thiol tethered peptide. These star polymers were well characterized using gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), electrospray ionization mass spectroscopy (ESI-MS) and dynamic light scattering (DLS). (C) 2009 Elsevier Ltd. All rights reserved.