Dual-Targeting Cascade Nanodelivery System for Precision Gastric Ulcer Therapy: Modular Green Synthesis, Anti-Inflammatory, and Antioxidant Synergy via CD44/Folate Receptor Targeting

Gastric ulcers, caused by factors such as H. pylori infection and NSAID misuse, are characterized by mucosal barrier erosion and severe complications. Current therapeutic approaches employing proton pump inhibitors, H 2 -receptor antagonists, antibiotics, and antacids face challenges, including reduced bone density, rising antibiotic resistance, and poor drug targeting. Here, we developed a dual-targeting oral nanodelivery system (CFLTM) with a size range of 100 nm to 450 nm and an average size of 335 nm using a cascade-targeting strategy. CFLTM combines folic acid and chondroitin sulfate to enhance targeting precision in an acidic gastric environment. It is loaded with tannic acid and magnolol for anti-inflammatory and antioxidant effects. The study shows that CFLTM exhibits exceptional targeting efficiency, with its dual-targeting uptake capability demonstrating a significant 1.21-fold enhancement compared to single-targeting systems. This enables rapid and precise localization to gastric ulcer sites while reducing oxidative stress and inflammation through modulation of key biomarkers. Using a green aqueous synthesis process, CFLTM achieves low energy consumption and high encapsulation efficiency. This innovative system shifts gastric ulcer treatment from passive acid suppression to active tissue repair, providing a new therapeutic approach and a platform for treating other digestive diseases.