Authors
Rui Fu, Qing Li, Guanzhong Zhao, Qingyan Gao, Huantong Chen, Khemayanto Hidayat, Jiaying Xu, Liqiang Qin, Chunhong Hu, Yu Chong, Su Hu
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e76146. Jun 15, 2026. Epub Jun 15, 2026.
Abstract
Pancreatic cancer exhibits extensive metabolic reprogramming that supports rapid progression and therapeutic resistance, making metabolic vulnerabilities attractive targets for intervention. Here, a tumor microenvironment-responsive nanoreactor (Pht@HMnO2-HA) is designed to induce disulfidptosis in pancreatic cancer through coordinated metabolic interference and redox catalysis. Following CD44-mediated tumor targeting and cellular internalization, the nanoreactor's responsive self-optimization within the tumor microenvironment enables localized release of phloretin, suppressing glucose uptake and pentose phosphate pathway activity and thereby limiting intracellular reducing-power generation. In parallel, the nanoreactor consumes intracellular glutathione and amplifies oxidative stress via MnO2-mediated redox reactions, thereby depleting antioxidant defenses. Together, these processes impose reducing-power deprivation and disrupt redox homeostasis, leading to cystine accumulation, disulfide stress, actin cytoskeleton collapse, and disulfidptosis in pancreatic cancer cells. Moreover, degradation-associated Mn2 + release provides activatable T1-weighted MRI contrast, enabling noninvasive visualization of intratumoral nanoreactor activation and therapeutic progression. Collectively, this work establishes a theranostic nanoreactor that exploits coupled metabolic and redox vulnerabilities to induce disulfidptosis, offering a mechanistically grounded strategy for precision therapy in pancreatic cancer.
PMID:
42295770
Bibliographic data and abstract were imported from PubMed on 15 Jun 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 5
- Comments 0