Glucose-responsive erythrocyte-bound nanoparticles for continuously modulated insulin release

Glucose-responsive closed-loop insulin delivery systems represent a promising treatment strategy for diabetes, but current systems generally cannot achieve long-term effects. In this study, we designed an erythrocyte-biomimetic glucose-responsive system (EGRS) by coupling glucose-responsive nanoparticles (GRNs) to red blood cells; these nanoparticles exhibited the dual functions of glucose-responsiveness and persistent presence in circulation. GRNs are generated by encapsulating with insulin through ion crosslinking, followed by coloading with glucose oxidase (GO(x)) and catalase (CAT), a process that endows the nanoparticles with glucose-responsiveness. Simultaneously, the GRNs are coupled with red blood cells to camouflage them from the immune system, therefore, these erythrocyte-coupled GRNs can circulate in the blood for a long time. Under conditions of hyperglycemia, GOx acts on blood glucose to produce gluconic acid, which causes the rupture of GRNs and efficient release of insulin. Conversely, insulin is only released at the basic rate during hypoglycemia. Thus, EGRS can efficiently and continuously respond to hyperglycemia to maintain blood glucose levels within the normal range.