Three-Day Blood Glucose Control via a Glucose Modulator of Glycopolymersome: Sugar versus Sugar

Natural modulators, such as insulin, play a significant role in modulating molecule levels. Inspired by the role of natural modulators, herein, we propose a glucose modulator that is composed of a glycopolymersome only to regulate glucose levels. This insulin- and drug-free strategy can smartly take in and snap out glucose according to the surrounding blood glucose levels (BGLs) by reversible sugar substituting. The glycopolymersome is self-assembled from a biodegradable glycopolymer that is composed of sugar and phenylboronic acid derivative, poly(epsilon-caprolactone)-block-poly[(3-acrylamidophenylboronic acid-stat-N-acryloyl glucosamine] [PCL-b-P(AAPBA-stat-AGA)]. It exhibits excellent long-term hypoglycemic effects toward type 1 diabetic mice for at least 3 days upon one shot without observed side effects, which is the longest effective sugar-regulation time for the insulin and drug-free strategy. Most notably, we explored the effect of the molecular structure of the glycopolymers on the BGL regulating efficacy, where the glucosyl moiety was polymerized with PBA either randomly or separately. Block-statistical glycopolymersomes exhibited lower binding energy to glucose, better glucose responsiveness, and prolonged hypoglycemic effect due to the abundant intramolecular and intermolecular dynamic covalent bonds between AAPBA and AGA. Our finding confirmed the importance of a block-statistical copolymer structure and the key role of sugar in regulating BGLs without involving medication, which may provide guidance and open new avenues for design blood glucose regulating materials.