Glucose and magnetic-responsive approach toward in situ nitric oxide bubbles controlled generation for hyperglycemia theranostics.

Stimuli-responsive devices that deliver drugs or imaging contrast agents in spatial-, temporal- and dosage-controlled fashions have emerged as the most promising and valuable platform for targeted and controlled drug delivery. However, implementing high performance of these functions in one single delivery carrier remains extremely challenging. Herein, we have developed a sequential strategy for developing glucose and magnetic-responsive microvesicle delivery system, which regulates the glucose levels and spatiotemporally controls the generation of nitric oxide gas free bubbles. It is observed that such injectable microvesicles loaded with enzyme and magnetic nanoparticles can firstly regulate hyperglycemic level based on the enzymatic reactions between glucose oxidase and glucose. In a sequential manner, concomitant magnetic field stimuli enhance the shell permeability while prompts the reaction between H2O2 and l-arginine to generate the gasotransmitters nitric oxide, which can be imaged by ultrasound and further delivered for diabetic nephropathy therapy. Therefore, magnetic microvesicles with glucose oxidase may be designed as a novel theranostic approach for restoring glucose homeostasis and spatiotemporally control NO release for maintaining good overall diabetic health.