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Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
Stiffness-tunable oral nanoparticles facilitate damaged islet β cell restoration for diabetes treatment
Wenyan She1,2,3, Xiaojuan Jiang1,2,3, Siying Deng1,2,3
1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
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.
Insights
This study introduces oral nanoparticles that repair islet beta cells by targeting oxidative stress in diabetes. The novel nanotherapy restores insulin homeostasis, offering a potential alternative to lifelong insulin treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Endocrinology
Background:
- Diabetes mellitus poses a global health challenge, with current insulin therapies managing blood glucose but not restoring pancreatic islet beta cell function.
- Existing antioxidant drugs for islet beta cell repair face limitations in oral bioavailability and targeted delivery to the pancreas.
Purpose of the Study:
- To identify ferroptosis-associated oxidative stress as a cause of islet beta cell death.
- To develop novel stiffness-gradient nanoparticles for enhanced oral delivery and pancreatic targeting of therapeutic agents.
- To evaluate the efficacy of the developed nanotherapy in restoring beta cell function and glycemic control in diabetic models.
Main Methods:
- Identification of ferroptosis-associated oxidative stress in islet beta cell death.
- Development of stiffness-gradient nanoparticles using oleic acid and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine.
- Assessment of nanoparticle transcytosis, macrophage-mediated uptake, and pancreatic accumulation.
- Evaluation of therapeutic effects in diabetic animal models, including glucose homeostasis and insulin secretion.
Main Results:
- Nanoparticles with intermediate stiffness demonstrated enhanced intestinal M cell transcytosis and macrophage-mediated transport, increasing pancreatic curcumin accumulation by approximately 4.5-fold.
- The nanotherapy effectively suppressed ferroptosis-associated oxidative stress in pancreatic islets.
- Restoration of insulin homeostasis and autonomous glycemic control was observed, maintaining normoglycemia without hypoglycemia.
Conclusions:
- Oral administration of stiffness-gradient nanoparticles represents a promising strategy for targeting pancreatic islets and delivering therapeutic agents.
- This nanotherapy promotes in situ islet beta cell repair and restores glycemic control, outperforming insulin therapy in long-standing diabetes models.
- The developed nanotherapy offers a patient-friendly, oral alternative for managing diabetes by addressing the underlying cause of beta cell dysfunction.
