Synthesis and volume phase transition of concanavalin A-based glucose-responsive nanogels

Glucose-responsive polymer nanogels that can undergo a reversible and rapid volume phase transition in response to the fluctuation in blood glucose concentration have the potential to regulate the delivery of insulin mimicking pancreatic activity. We report here such a glucose-responsive polymer nanogel, which is made of concanavalin A (ConA) interpenetrated in a chemically crosslinked network of poly(N-isopropylacrylamide) (poly(NIPAM)). The introduction of ConA, a plant lectin protein, into the poly(NIPAM) network makes the newly developed semi-interpenetrating-structured nanogels responsive to glucose over a glucose concentration range of 0–20 mM at a physiological pH of 7.4. While the nanogels can swell and become stable shortly (<1 s) after adding glucose over a concentration range of 50.0 μM to 20.0 mM, the changes in the average hydrodynamic radius and the size distribution of the nanogels can be fully reversible within the experimental error even after ten cycles of adding/removing glucose. The association rate constant is determined to be ca. 1.8 mM−1 s−1, and the dissociation rate constant is ca. 7.5 s−1, indicating a fast reversible time response to the glucose concentration change of the nanogels. Moreover, in vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations.