Pancreatitis is characterised by oxidative stress and irritation and continuously coexists with diabetes mellitus (DM), a metabolic dysfunction with dysregulated glucose homeostasis. Nevertheless, built-in therapies stay elusive [1], [2], [3], [4], [5], [6], [7], [8], [9]. Present therapies for pancreatitis give attention to symptom administration, whereas diabetes depends closely on insulin, a remedy linked to pancreatic fats accumulation and illness development [10], [11], [12], [13], [14]. A important want exists for insulin-free methods that concurrently handle hyperglycemia and irritation with out exogenous medicine.
Glucose-responsive supplies, significantly these leveraging boronic acid-diol dynamic covalent bonds, supply promise for glucose regulation [15], [16], [17], [18], [19], [20]. Nevertheless, present programs typically lack biocompatibility, sustained efficacy, or twin therapeutic performance. Equally, whereas ROS-scavenging nanomaterials have been explored for pancreatitis [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], their scientific translation is hindered by poor focusing on and single-mechanism motion. To bridge these gaps, an built-in technique that mixes glucose sensing, ROS scavenging, and tissue focusing on is urgently wanted to deal with the problem.
Herein, we current a flexible “drug-free” glycopolymersome platform that mixes blood glucose regulation and antioxidant bioactivity in a single triblock glycopolymer for the synergistic remedy of diabetes and pancreatitis (Fig. 1). Not like prior works, our design integrates: (1) A P(AAPBA-stat-AGA) block for reversible, concentration-dependent glucose responsiveness, enabling bidirectional glucose uptake and launch. (2) A PAEMA spine post-functionalized with phenolic antioxidants (ferulic acid or tyrosine) by way of amidation, reaching ROS elimination with out compromising polymersome stability. (3) Pancreas-targeted accumulation, validated by biodistribution research, to maximise therapeutic efficacy. These antioxidant glycopolymersomes enabled sturdy blood glucose regulation with 60 h normoglycemia and irritation discount in diabetic and pancreatitis murine fashions. General, this work gives invaluable insights into synergistic “drug-free” therapies for metabolic problems and diabetes-related issues, aiming to attain optimum glycemic management whereas minimizing pancreatic stress.
