A quantitative design framework for ROS-responsive, hypersensitive materials targeting pancreatic β cells

• Quantitative framework for ROS-responsive β cell targeting design. • Specificity index guides selective drug release under pathological ROS. • Provides theoretical basis for optimizing material performance and safety. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by insulin (INS) resistance and progressive pancreatic β cell degeneration.Reactive oxygen species (ROS) play a pivotal role in the pathological progression of T2DM,where elevated ROS levels contribute to oxidative stress,exacerbating β cell damage and apoptosis. This oxidative stress.however, creates a distinct‘niche’ signal that can be leveraged for targeted drug delivery to pancreatic β cells using ROS responsive materials.Given this, drug delivery systems based on ROS-sensitive materials have emerged as a promising approach for T2DM therapy,offering selective and localized release capabilities at the lesion site. This study establishes a quantitative theoretical framework for designing ROS-sensitive materials to target pancreatic β cells,integrating pathological microenvironment (niche) quantification, material response dynamics,and drug release models to optimize therapeutic outcomes for T2DM. By defining a pathological ROS window and introducing a threshold-matching principle,the framework enables predictive optimization of material responsiveness and therapeutic specificity,while addressing challenges related to off-target effects and therapeutic efficiency.This study aims to bridge pathological microenvironment analysis with rational materials design, providing a theoretical basis for engineering ROS-responsive systems with disease-specific activation thresholds.