Thermoresponsive biotinylated star amphiphilic block copolymer: Synthesis, self-assembly, and specific target recognition

A novel star amphiphilic block copolymer star poly(epsilon-caprolactone)-b-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-DDAT [SPCL-b-P(NIPAAm-co-DMAAm)-DDAT] (DDAT: S-1-dodecyl-S'-(alpha,alpha'-dimethyl-alpha-acetic acid)trithiocarbonate) was synthesized by combination of ring-opening polymerization (ROP) and reversible addition-fragment chain transfer (RAFT) polymerization. DDAT-terminated groups were further transformed into hydroxyl groups by one-pot strategy for aminolysis of DDAT and Michael addition reaction of an alpha,beta-unsaturated ester of 2-hydroxyethyl acrylate (HEA). Biotinylated star copolymer SPCL-b-P(NIPAAm-co-DMAAm)-Biotin was obtained by coupling of biotin to the hydroxyl-terminated star copolymer using carbodiimide coupling chemistry. These star copolymers with DDAT, hydroxyl, and biotin end groups were capable of self assembling into core-shell structural micelles in aqueous solution. The variation of end groups significantly affected the micellar characters, such as hydrodynamic diameter (D-h), critical micellar concentration (CMC), and lower critical solution temperature (LCST). Biotinylated micelle exhibited a phase transition at 41.4 degrees C. The amount of biotin on the micelle surface as well as the specific recognition between biotinylated micelle and avidin was determined by 4'-hydroxyazobenzene-2-carboxylic acid/avidin (HABA/avidin) binding assay and dynamic light scattering (DLS). In addition, the biotinylated star copolymer displayed good biocompatibility according to a preliminary cytotoxicity study. The novel polymeric micelle with biodegradability, thermoresponse, and specific target recognition was expected to be a promising polymeric carrier material for targeted drug delivery. (C) 2012 Elsevier Ltd. All rights reserved.