A Versatile Tool for Imaging Neutrophil Elastase in Diabetic Complication

Diabetes mellitus is a chronic metabolic disorder associated with persistent hyperglycemia, leading to severe complications affecting multiple organs, particularly the liver and wound healing processes. One major factor driving these complications is neutrophil elastase (NE), a protease that plays a pivotal role in inflammation and impaired tissue repair. Despite its crucial involvement, detecting NE activity in vivo has been challenging due to limitations in current detection methods. This study introduces a novel NE-specific probe, NEP, and its self-assembled form, NanoNEP, designed to overcome these challenges. NanoNEP was synthesized by assembling NEP with bovine serum albumin (BSA) to enhance its biocompatibility, solubility, and dispersion. The probe was characterized for its selectivity, stability, and biocompatibility, and demonstrated its ability to monitor NE activity in vivo, specifically in diabetic mice liver, wounds, and serum, as well as in human diabetic foot lesions. These findings highlight the potential of NanoNEP as a sensitive and innovative tool for real-time detection of NE activity, providing valuable insights into the pathogenesis of diabetes-related complications and offering new opportunities for improved diagnostic and therapeutic strategies.