Corrole-based Photothermal Nanocomposite Hydrogel with Nitric Oxide Release for Diabetic Wound Healing.

Abstract

The management of chronic diabetic wounds remains a significant challenge due to persistent bacterial infections and impaired angiogenesis. Herein, we reported a nanocomposite hydrogel (M/P-SNO/G) incorporated with M/P-SNO nanoparticles engineered by supramolecular assembly of the photosensitizing mono-carboxyl corrole (MCC) and S-nitrosothiol-modified polyethylene glycol (mPEG-SNO) for synergistic photothermal therapy (PTT)/nitric oxide (NO) treatment of diabetic wounds. The strong π-π interaction among aggregated MCC in M/P-SNO enhances the optical absorption and photothermal ability, thereby facilitating the precise release of NO upon laser irradiation. The hydrogel matrix, composed of oxidized hyaluronic acid and carboxymethyl chitosan crosslinked by Schiff-base, demonstrates good injectability and self-healing characteristics, providing an ideal environment for wound repair. As expected, M/P-SNO/G exhibits a desirable photothermal performance and a controlled laser-responsive NO release, realizing enhanced bactericidal effect and anti-biofilm ability in vitro. In a full-thickness skin defect model on diabetic mice, M/P-SNO/G has proven effective in bacteria clearance and angiogenesis, significantly accelerating wound healing. This study presents a feasible supramolecular strategy to develop diabetic wound dressings with synergistic PTT/NO treatment. STATEMENT OF SIGNIFICANCE: Developing advanced dressings that simultaneously eliminate bacteria and accelerate wound recovery is essential for treating diabetic wounds. This study developed a nanocomposite hydrogel (M/P-SNO/G) featuring the synergistic effect of photothermal therapy (PTT) and nitric oxide (NO) treatment to accelerate infected diabetic wound healing. M/P-SNO NPs within the hydrogel are self-assembled through the hydrophobic photosensitizing mono-carboxyl corrole (MCC) and the hydrophilic NO-releasing polymer (mPEG-SNO), where highly aggregated MCC molecules ensure superior photothermal performance. Meanwhile, the temperature increase induced by the photothermal effect activates NO release from the hydrogel. Under 660 nm laser irradiation, M/P-SNO/G demonstrates a PTT/NO synergy to effectively inhibit bacterial proliferation and promote angiogenesis, offering significant benefits in diabetic wound repair and further expanding the biomedical applications of corroles.