Ultrasound-Triggered On-Demand Insulin Release for Diabetes Mellitus Treatment.

Exogenous insulin (INS) is successfully used for controlling glucose in diabetic patients. Although frequent INS injections can overcome hyperglycemia, they are both painful and inconvenient. Herein, we report an ultrasound-regulated INS release platform (INS-PPIX@ER hydrogel) that allows for remotely regulated on-demand INS release and minimizes pain. In this system, protoporphyrin IX (PPIX)-containing erythrocytes (ERs) served as an INS reservoir, an injectable peptide hydrogel provided strong protection for the ERs, and INS release was regulated using ultrasound. This particular INS release behavior was triggered by increased production of reactive oxygen species (ROS) by PPIX from the PPIX-loaded ERs under ultrasound irradiation. The ROS then interacted with the phospholipid bilayer of the ERs, thereby opening the stomata of the INS-PPIX@ER and releasing INS. INS-PPIX@ER hydrogels could control hyperglycemia within 2 h and maintained normal blood glucose levels for up to 3 days. This effective remote approach allowed closed-loop drug release spatiotemporally without causing any pain and injury. Our findings could serve as a powerful tool for constructing a precisely controlled release system.