A Multifunctional Nanozyme-Based mRNA Delivery Platform Restores Neurovascular and Sudomotor Function in Diabetic...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Nanotechnology

Background:

• Diabetic sudomotor dysfunction, a common complication of diabetic neuropathy, impairs sweat gland function.
• Current treatments for this condition are limited, highlighting the need for innovative therapeutic strategies.

Purpose of the Study:

• To develop and evaluate a multifunctional nanozyme-based platform for delivering nerve growth factor (NGF)-encoding mRNA.
• To restore sweat gland function and address the pathological microenvironment in diabetic neuropathy.

Main Methods:

• A nanozyme platform (Au@Pt-PGEA, APP) was engineered for mRNA delivery.
• APP possesses glucose oxidase-like activity, scavenges reactive oxygen species, generates oxygen, and has electroactive properties.
• The APP/NGF mRNA complex (APPN) was tested in vitro and in a late-stage diabetic neuropathy mouse model.

Main Results:

• APPN promoted endothelial angiogenic responses, Schwann cell activation, and neurite outgrowth in vitro.
• In vivo, APPN treatment improved perfusion, sweat output, and neurovascular reconstruction in diabetic mice.
• APPN restored sweat gland structure and function, shifting gene expression towards reduced inflammation and enhanced regeneration.

Conclusions:

• Multifunctional nanozyme-mediated gene therapy offers a promising strategy for diabetic sudomotor dysfunction.
• This approach demonstrates significant potential for regenerative medicine and treating peripheral nervous system complications.