Doubly responsive polymersomes towards monosaccharides and temperature under physiologically relevant conditions

Organoboronic acid-containing polymers and block copolymers have recently attracted attention because of their ability to recognize important natural diol compounds such as saccharides and nucleotides under physiologically relevant conditions at neutral pH. In particular, polymers and block copolymers that are responsive toward multiple stimuli can be utilized to create smart delivery vehicles for use in applications in a complex environment. Here we report the monosaccharide-responsive polymers and block copolymers comprising styreneboroxole and oligo(ethylene glycol)-functionalized styrenes (OEG-STs) as repeating units. We have shown that homopolymers and copolymers of OEG-STs are thermally responsive by demonstrating that they possess the characteristic of tunable lower critical solution temperature (LCST) in water. When copolymerized with OEG-STs, styreneboroxole units function as a switch to change the solubility of the resulting polymers in aqueous solution by recognizing mono-saccharides via the formation of boronate ester. By introducing the minimum number of monosaccharide-responsive styreneboroxole units onto the thermally responsive OEG-ST backbone, we demonstrated the monosaccharide-responsive behavior of the resulting copolymers and their amphiphilic block copolymers in aqueous solution at physiologically relevant pH and temperature. A strategy based on doubly responsive block copolymers reported here could be utilized as new delivery vehicles for cargo molecules such as insulin, due to their ability to function in an in vivo environment.