Glucose-sensitive glycopolypeptide nanocarriers equipped with glucose oxidase for self-regulated insulin release

Smart responsive nanocarriers are widely used for the self-regulated release of insulin. However, their development is still constrained by slow response speed and poor biocompatibility. Here, based on the dynamic covalent bonds between phenylboronic acids and diols, phenylboronic acid-functionalized polypeptide poly(ethylene glycol)-b-poly-(aspartic acid-co-aspartamidophenylboronic acid) (PEG-b-P(Asp-co-AspPBA)) and dextran were directly mixed to form glycopolypeptide nanoparticles. Meanwhile, insulin and glucose oxidase (GOx) were loaded during nanoparticle formation to construct rapidly glucose-responsive nanocarriers, which could be destroyed by glucose and H2O2 generated from the glucose–GOx system. Dynamic light scattering studies and insulin release analyses confirmed that these nanoparticles exhibited dual sensitivity to glucose and H2O2. Evaluation of blood glucose regulation in diabetic mice demonstrated that the group treated with insulin–GOx-loaded glycopolypeptide nanoparticles sharply reached the normoglycemic state within 0.5 h and maintained it for up to 13 h. Furthermore, cytotoxicity assessments, hemolysis experiments, and histopathological analyses confirmed the excellent biocompatibility of the nanoparticles. Therefore, this nanoparticle drug delivery system holds great promise for diabetes treatment.