Charge-switching, amphoteric glucose-responsive microgels with physiological swelling activity

Amphoteric, poly(N-isopropylacrylamide)-based microgels are functionalized with aminophenylboronic acid (PBA) functional groups to produce colloidally stable, glucose-responsive gel nanoparticles that exhibit glucose-dependent swelling responses at physiological temperature, pH, and ionic strength. Up to 2-fold volumetric swelling responses are observed in response to physiological glucose concentrations, the first such physiological response reported for a colloidally stable microgel. Amphoteric microgels can also be designed to both swell and deswell in response to glucose according to the pH of the medium, the concentration of PBA groups grafted to the microgel, and the relative concentrations of the cationic and anionic functional groups in the platform microgel. The increasing anionic charge density on the microgels observed at higher glucose binding fractions can be applied to switch the net charge of the microgels from cationic to anionic as the glucose concentration increases. Preliminary experiments suggest that such amphoteric PBA-microgels have a high capacity for insulin uptake and can selectively release more insulin at higher glucose concentrations under physiological conditions via glucose-induced, "on-off" switching of electrostatic attractions between insulin and the microgel.