Ultrafast glucose-responsive, high loading capacity erythrocyte to self-regulate the release of insulin.

Insulin (INS) delivery system that can mimic normal insulin secretion to maintain the blood glucose level (BGL) in the normal range is an ideal treatment for diabetes. However, most of the existing closed-loop INS delivery systems respond slowly to the changes in BGL, resulting in a time lag between the abnormal BGL and the release of INS, which is not suitable for practical application. In this study, glucose oxidase (GOx)-modified erythrocytes are used as INS carriers (GOx-INS-ER) that can rapidly self-regulate the release of INS upon the changes in BGL. In this system, glucose can be broken down into gluconic acid and hydrogen peroxide by GOx-INS-ER, and the latter will rupture the erythrocyte membrane to release INS within minutes. A pulsatile release of INS can be achieved upon the changes in the glucose concentration. This GOx-INS-ER enables diabetic rats to overcome hyperglycemia within 1 h, and a single injection of this GOx-INS-ER into the STZ-induced diabetic rats can maintain the BGL in the normal range up to 9 days. STATEMENT OF SIGNIFICANCE: Diabetes mellitus has been a major public health threatener with global prevalence. Although, glucose-responsive carriers that can release insulin (INS) in a closed loop have been explored greatly in recent years, their sluggish glucose-responsive property and low INS-loading content greatly restrict their practical application [ACS Nano, 2013, 7, 4194]. In this work, we reported INS-loaded erythrocytes featuring ultrafast glucose-responsive property and high INS loading content, which could release INS in a closed loop. These GOX-INS-ERs could respond to the changes in glucose level within several minutes and self-regulate the release of INS for a long time. Single injection of GOX-INS-ER can overcome hyperglycemia in diabetic mice within 1 h and maintain the baseline level of glucose up to 9 days. We think our method may provide a robust way to potentiate diabetes treatment.