Glycopolypeptide Nanocarriers Based on Dynamic Covalent Bonds for Glucose Dual-Responsiveness and Self-Regulated Release of Insulin in Diabetic Rats.

Abstract

An intelligent carrier system is based on fast glucose response mechanism to regulate the insulin release. Here, glucose dual-responsive nanoparticles were quickly and efficiently obtained, by dynamic covalent bonds between phenylboronic acid-containing homopolymer poly(3-acrylamidophenylboronic acid) (PAAPBA) and glycopolypeptide poly(ethylene glycol)-b-poly(aspartic acid-co-aspart-glucosamine) (PEG-b-P(Asp-co-AGA)) through the formation of cycloborates. Meanwhile, insulin and glucose oxidase (GOx) were loaded during the formation of nanoparticles. The cycloborates in the nanoparticles could be destroyed by the replacement of glycosyl moieties by glucose and oxidized by H2O2 generated from the glucose-GOx system, resulting in the rapid insulin release. After subcutaneous delivery of the insulin/GOx-loaded nanoparticles to diabetic mice, a significant hypoglycemic effect was observed over time. Cytotoxicity study, hemolysis assay, and histological analyses suggested that the nanoparticles showed excellent biocompatibility and safety. This work lays the important theoretical and technical foundations for expanding the scope of applications of nanocarriers in diabetes treatment.