Yang Haixia, Chen Qing, Qiang Huaqiong, Wang Bo, Chen Junyang, Xie Yingling, Peng Liyan, Zhao Huanhuan, Tian Jian
Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
The Affiliated Hospital of Hubei Provincial Government (Hubei Rehabilitation Hospital), Wuhan 430071, China.
Acta Biomater. 2025 Jan 15;192:431-445. doi: 10.1016/j.actbio.2024.12.020. Epub 2024 Dec 9.
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 nanoparticles 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.
由于持续的细菌感染和血管生成受损，慢性糖尿病伤口的管理仍然是一项重大挑战。在此，我们报道了一种纳米复合水凝胶（M/P-SNO/G），其包含通过光敏单羧基卟啉（MCC）和S-亚硝基硫醇修饰的聚乙二醇（mPEG-SNO）的超分子组装工程化的M/P-SNO纳米颗粒，用于糖尿病伤口的协同光热疗法（PTT）/一氧化氮（NO）治疗。M/P-SNO中聚集的MCC之间强烈的π-π相互作用增强了光吸收和光热能力，从而促进了激光照射时NO的精确释放。由席夫碱交联的氧化透明质酸和羧甲基壳聚糖组成的水凝胶基质具有良好的可注射性和自愈特性，为伤口修复提供了理想的环境。正如预期的那样，M/P-SNO/G表现出理想的光热性能和可控的激光响应性NO释放，在体外实现了增强的杀菌效果和抗生物膜能力。在糖尿病小鼠的全层皮肤缺损模型中，M/P-SNO/G已被证明在清除细菌和促进血管生成方面有效，显著加速了伤口愈合。本研究提出了一种可行的超分子策略，以开发具有协同PTT/NO治疗的糖尿病伤口敷料。重要性声明：开发同时消除细菌并加速伤口恢复的先进敷料对于治疗糖尿病伤口至关重要。本研究开发了一种具有光热疗法（PTT）和一氧化氮（NO）治疗协同作用的纳米复合水凝胶（M/P-SNO/G），以加速感染的糖尿病伤口愈合。水凝胶中的M/P-SNO纳米颗粒通过疏水性光敏单羧基卟啉（MCC）和亲水性NO释放聚合物（mPEG-SNO）自组装，其中高度聚集的MCC分子确保了优异的光热性能。同时，光热效应引起的温度升高激活了水凝胶中NO的释放。在660nm激光照射下，M/P-SNO/G表现出PTT/NO协同作用，有效地抑制细菌增殖并促进血管生成，在糖尿病伤口修复中具有显著益处，并进一步扩展了卟啉的生物医学应用。
