posted on 2024-01-26, 11:04authored byYufen Xiao, Jiamin Zhang, Tong Wu, Shuai Chen, Zhixiong Huang, Jianzhong Du
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(ε-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.