Diverse thermoresponsive behaviors of uncharged UCST block copolymer micelles in physiological medium

Three amphiphilic diblock copolymers, representative of three types of block copolymer (BCP) design, were synthesized using reversible addition-fragmentation chain-transfer (RAFT) polymerization. All of them have a same uncharged block of a random copolymer of commercially available acrylamide and acrylonitrile, P(AAm-co-AN), and exhibit a composition-tunable upper critical solution temperature (UCST). We show that by coupling a common P(AAm-co-AN) block with either hydrophobic polystyrene (PS) or hydrophilic poly(dimethylacrylamide) (PDMA) or the lower critical solution temperature (LCST) polymer of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), the BCP micelles formed in water or in phosphate buffered saline (PBS) can display diverse and UCST-dictated changes in response to temperature variations, such as the reversible dispersion-aggregation of micelles, dissolution-formation of micelles, and reversal of micelle core and corona. The results point out that P(AAm-co-AN) is a robust UCST polymer that can be introduced into controlled polymer architectures producible by RAFT, the same way as using the extensively studied LCST counterparts like poly(N-isopropylacrylamide) (PNIPAM). This ability should make the door wide open to exploring new thermosensitive polymers based on the thermosensitivity opposite to the LCST.