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

Abstract

A novel star amphiphilic block copolymer star poly(ε-caprolactone)-b-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-DDAT [SPCL-b-P(NIPAAm-co-DMAAm)-DDAT] (DDAT: S-1-dodecyl-S′-(α,α′-dimethyl-α″-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 α,β-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 (Dh), critical micellar concentration (CMC), and lower critical solution temperature (LCST). Biotinylated micelle exhibited a phase transition at 41.4 °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.