Hemoglobin integrated red blood cell membrane-coated metal-organic framework nano-platform for improving the self-adaptive blood glucose management

Diabetes, a prevalent chronic metabolic disorder, often leads to severe complications. Currently, existing treatment methods may pose life-threatening risks due to poor patient compliance and inaccurate dosing of subcutaneous insulin injections. Hence, a biomimetic red blood cell (RBC) membrane-coated glucose-responsive nanoplatform is developed for controlling insulin release. Functionalizing nanoplatforms with RBC membrane can prolong the half-life of nano-formulation in vivo mediated by the biomimetic immune escape. Simultaneously, the cascade catalytic effect of glucose oxidase (GOx) encapsulated in metal-organic frameworks (MOFs) and hemoglobin (Hb) in the RBC membrane are able to not only facilitate glucose-responsive insulin release, but also eliminate the detrimental by-product hydrogen peroxide (H₂O₂) resulting from the Hb mediated H₂O₂ scavenging. Both in vitro and in vivo studies have demonstrated the favorable glucose-responsive performances of this advanced nano-platform with a single intravenous injection maintaining blood glucose balance in Type 1 Diabetes (T1D) mice for an extended duration without the hypoglycemia risk. Therefore, this biomimetic insulin delivery system is poised to function as a strategy for the intravenous insulin administration, offering a promising drug candidate for the self-adaptive long-term T1D treatment.