Glucose-Triggered Micellization of Poly(ethylene glycol)-b-poly(N-isopropylacrylamide-co-2-(acrylamido)phenylboronic acid) Block Copolymer

Many glucose-sensitive micelles self-assembled from phenylboronic acid (PBA)-functionalized block copolymers have been reported; however, the addition of glucose always triggers the disassembly of the micelles. Herein, we reported a glucose-sensitive micelle of poly(ethylene glycol)-b-poly(N-isopropylacrylamide-co-2-(acrylamido)phenylboronic acid) (PEG-b-P(NIPAM-2-AAPBA)) block copolymer that responds to glucose in a very different way. Using a macro-reversible addition-fragmentation chain transfer (RAFT) agent, the block copolymer was synthesized by RAFT copolymerization of NIPAM and 2-AAPBA. Because of the thermosensitivity of the P(NIPAM-2-AAPBA) block, the copolymer self-assembles into micelles upon heating. More importantly, the addition of glucose triggers the micellization of the copolymer instead of disassembly of the micelles. The unique behavior of PEG-b-P(NIPAM-2-AAPBA) originates from the unique glucose-responsive mechanism of the P(NIPAM-2-AAPBA) block. For common PBA-functionalized polymers, reaction with glucose results in more ionized form of the PBA group, turns the polymer from hydrophobic to hydrophilic, and thus leads to the disassembly of the micelles. Very differently, for P(NIPAM-2-AAPBA), adding glucose lowers its lower critical solution temperature (LCST), turns it from hydrophilic to hydrophobic, and therefore triggers the micellization of the block copolymer. Besides glucose, sugars such as fructose, mannose, and galactose can trigger the self-assembly of PEG-b-P(NIPAM-2-AAPBA) too.