Glucose-Activated Nanoreactor Initiating Cascade Reaction to Remodel Immune Microenvironment for Promoting Diabetic...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Regenerative Medicine

Background:

• Diabetic wound healing is complex, involving hyperglycemia, hypoxia, and oxidative stress.
• Single-enzyme therapies are insufficient for addressing these interconnected issues.
• A coordinated approach is needed to remodel the diabetic wound microenvironment.

Purpose of the Study:

• To develop an integrated nanozyme system (MCP@G) for simultaneous management of hyperglycemia, hypoxia, and oxidative stress in diabetic wounds.
• To investigate the therapeutic efficacy of MCP@G in vitro and in vivo.
• To establish a multienzyme mimicking strategy for refractory diabetic wound treatment.

Main Methods:

• Integration of glucose oxidase (GOx) with a Pt-deposited Mn-doped Ce metal-organic framework (MOF) nanozyme.
• Development of a cascade reaction involving GOx, superoxide dismutase (SOD)-mimic, and catalase (CAT)-mimic activities.
• In vitro and in vivo evaluation of MCP@G's effects on oxidative stress, inflammation, cell migration, angiogenesis, and wound closure in diabetic models.

Main Results:

• MCP@G successfully created a self-enhancing cascade reaction, consuming glucose and oxygen while mitigating oxidative stress and generating oxygen.
• In vitro and in vivo studies showed MCP@G alleviated mitochondrial oxidative stress, modulated anti-inflammatory factors, and enhanced fibroblast migration.
• MCP@G treatment significantly accelerated wound closure, promoted collagen deposition, and induced hair follicle regeneration in diabetic rats.

Conclusions:

• The integrated nanozyme system MCP@G effectively remodels the diabetic wound microenvironment by addressing hyperglycemia, hypoxia, and oxidative stress.
• MCP@G demonstrates significant therapeutic potential for accelerating diabetic wound healing and tissue regeneration.
• This multienzyme mimicking strategy offers a promising platform for treating challenging diabetic wounds.