Stiffness-tunable oral nanoparticles facilitate damaged islet β cell restoration for diabetes treatment.

Authors

Wenyan She, Xiaojuan Jiang, Siying Deng, Luyuan Hu, Chenxi Huang, Lin Hou

Published in

Science advances. Volume 12. Issue 28. Pages eaed0407. Jul 10, 2026. Epub Jul 08, 2026.

Abstract

Diabetes mellitus remains a global health challenge, as current insulin-based therapies merely control blood glucose without restoring islet β cell function, leaving patients dependent on lifelong medication and vulnerable to hypoglycemia. Antioxidant drugs hold promise for islet β cell repair but are limited by poor gastrointestinal transportation and insufficient pancreatic targetability. Here, we initially identify ferroptosis-associated oxidative stress as a key cause of islet β cell death and develop six stiffness-gradient nanoparticles by embedding bent oleic acid into ordered 1,2-distearoyl-sn-glycero-3-phosphoethanolamine to enhance drug bioavailability. Nanoparticles with intermediate stiffness optimize membrane wrapping and minimize energetic cost, enhancing intestinal M cell transcytosis and macrophage-mediated hitchhiking, thereby increasing pancreatic curcumin accumulation by ~4.5-fold. In diabetic models, this formulation suppresses ferroptosis-associated oxidative stress, promotes in situ islet β cell repair, and restores insulin homeostasis and autonomous glycemic control, maintaining normoglycemia without hypoglycemia even after treatment cessation. This study represents a patient-friendly oral nanotherapy that outperforms insulin therapy in long-standing diabetes management.

PMID:
42418583
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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