Acid-responsive CST@NPs enhanced diabetic wound healing through rescuing mitochondrial dysfunction.

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Nanotechnology

Background:

• Diabetic ulcers (DUs) are severe diabetes complications, leading to poor outcomes.
• Cortistatin (CST) levels are decreased in DU skin, suggesting a therapeutic role.
• Current treatments for DUs often face challenges in efficacy and localized delivery.

Purpose of the Study:

• To develop an acid-responsive nanoparticle system for targeted delivery of cortistatin (CST) to diabetic wounds.
• To investigate the efficacy of CST-loaded nanoparticles in promoting diabetic wound healing.
• To evaluate the therapeutic potential of localized, acid-triggered CST release.

Main Methods:

• Preparation of cortistatin-loaded poly(N,N-dimethylacrylamide)-poly(2-ethylperfluorooctanesulfonamide) nanoparticles (CST@NPs).
• Assessment of nanoparticle acid-responsiveness and drug release kinetics.
• In vitro evaluation of CST@NPs on human umbilical vein endothelial cells (HUVECs) for oxidative stress and apoptosis.
• In vivo studies on diabetic rat models to assess wound healing, re-epithelialization, collagen deposition, angiogenesis, and inflammation.

Main Results:

• CST@NPs demonstrated rapid CST release in acidic environments, characteristic of wound sites.
• In vitro studies showed CST@NPs alleviated oxidative stress and reduced apoptosis in HUVECs.
• In vivo results indicated accelerated wound re-epithelialization, increased collagen deposition, and enhanced angiogenesis.
• CST@NPs effectively reduced local inflammation in diabetic wound models.

Conclusions:

• Acid-responsive CST@NPs provide a targeted and efficient delivery system for treating diabetic wounds.
• The nanoparticle system effectively promotes diabetic wound healing by modulating cellular processes and inflammatory responses.
• This nanotechnology-based approach offers a promising therapeutic strategy for chronic diabetic wound management.