Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.
Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.
J Transl Med. 2024 Nov 26;22(1):1066. doi: 10.1186/s12967-024-05875-4.
Traditional methods for treating diabetic wounds are limited in effectiveness because of their long healing times, the risk of immune rejection, and susceptibility to infection. Suppressing neutrophil extracellular traps (NETs) is an effective strategy for reducing persistent inflammation in diabetic wounds. Although disulfiram (DSF) can inhibit the significant increase of NETs in diabetic wounds, oral DSF suffers from rapid and harmful metabolism in the liver. To address these challenges, we developed a nanomedicine formulation in which DSF was incorporated into the hydrogel.
In this study, we developed a DSF-laden sodium alginate hydrogel wound dressing, DEP@SA, and characterized its composition, properties, and performance. We examined the effects of DEP@SA on inflammatory phase-related markers such as NETs and their pathway proteins, inflammatory factors, and macrophage phenotypes in a high-glucose environment in vivo and in vitro. In addition, the effects of DEP@SA on tissue regenerative capacity such as epidermal proliferative migration and angiogenesis, were also assessed.
The results showed that by utilizing extracellular vesicles as a drug delivery system, we effectively mitigated the degradation of DSF via direct contact with aqueous solutions and ensured the stability of DSF@SA, which could then be applied to diabetic wounds. The inflammatory phase-related indicators revealed that DSF@SA effectively reduced inflammation levels, decreased NETs formation, suppressed the Caspase-1/GSDMD pathway in neutrophils, and promoted the polarization of M2 macrophages. Moreover, the hydrogel accelerated wound healing by promoting angiogenesis and re-epithelialization, thereby shortening the diabetic wound healing time.
This study confirmed that the DSF@SA composite dressing has the potential to enhance diabetic wound repair and offers a novel approach for drug reutilization.
由于愈合时间长、免疫排斥风险和易感染等问题，传统的糖尿病创面治疗方法效果有限。抑制中性粒细胞胞外诱捕网（NETs）的形成是减少糖尿病创面持续炎症的有效策略。虽然戒酒硫（DSF）可以抑制糖尿病创面中 NETs 的大量增加，但口服 DSF 在肝脏中会迅速发生有害代谢。为了解决这些挑战，我们开发了一种纳米医学制剂，将 DSF 纳入水凝胶中。
在这项研究中，我们开发了一种负载 DSF 的海藻酸钠水凝胶伤口敷料，即 DEP@SA，并对其组成、性质和性能进行了表征。我们在体内和体外高糖环境中研究了 DEP@SA 对炎症相相关标志物（如 NETs 及其途径蛋白、炎症因子和巨噬细胞表型）的影响。此外，还评估了 DEP@SA 对组织再生能力（如表皮增殖迁移和血管生成）的影响。
结果表明，通过利用细胞外囊泡作为药物传递系统，我们有效地减轻了 DSF 与水溶液直接接触时的降解，并确保了 DSF@SA 的稳定性，使其能够应用于糖尿病创面。炎症相相关指标表明，DSF@SA 能有效降低炎症水平，减少 NETs 的形成，抑制中性粒细胞中 Caspase-1/GSDMD 途径，并促进 M2 巨噬细胞的极化。此外，该水凝胶通过促进血管生成和再上皮化加速了伤口愈合，从而缩短了糖尿病创面的愈合时间。
本研究证实，DSF@SA 复合敷料具有增强糖尿病创面修复的潜力，为药物再利用提供了一种新方法。
