A novel class of thermoresponsive and reduction-sensitive polymer, p(PEG-MEMA-co-Boe-Cyst-MMAm), containing disulfide linkages and removable hydrophobic tert-butyloxycarbonyl side chains was synthesized. The cloud points (CP) of p(PEG-MEMA-co-Boc-Cyst-MMAm) in water determined by UV/VlS spectrometer were between 20 degrees C and 57 degrees C, which shows that the CP can be tuned by adjusting the copolymer composition. Moreover, the thermosensitive polymers p(PEG-MEMA-co-Boc-Cyst-MMAm) formed stable nanoparticles in neutral aqueous medium, but rapidly destabilized in an reductive environment mimicking the intracellular space making them suitable for cytoplasmic drug delivery. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5989-5997, 2009