Chen Mengxia, Liu Ting, Wang Xiaonan, Gao Lizeng, Cheng Yunqing, Jiang Jing, Zhang Jinhua
College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China.
School of Life Sciences, Jilin Normal University, Jilin, 136000, China.
J Nanobiotechnology. 2025 May 13;23(1):342. doi: 10.1186/s12951-025-03396-w.
Wound healing requires coordinated progression through multiple programmed phases including hemostasis, infection control, inflammatory resolution, proliferation, and tissue remodeling. Many nanomaterials have shown great potential to promote wound healing, however, most of them only address partial aspects of these processes, making a recovery hard with adequate effects. In this study, we prepared a complex of nano-iron sulfide integrated with erythrocyte-templated nanozyme (ETN) (ETN@FeS) for comprehensive treatment of wounds. Firstly, ETN served as a mediator to confine iron sulfide to form FeS nanocomposite in a solvothermal reaction. Secondly, the ETN@FeS demonstrated bactericidal effects against methicillin-resistant Staphylococcus aureus (MRSA) by releasing ferrous iron and polysulfide to induce ferroptosis-like cell death. Thirdly, ferrous iron along with polysulfide exerted anti-inflammatory effects by inhibiting the activation of the NF-κB signaling pathway, while the polysulfide also contributed to angiogenesis by promoting the activation of vascular endothelial growth factor A (VEGFA), initiated phosphorylation-mediated activation of the PI3K/AKT signaling pathway, a master regulatory cascade governing endothelial cell survival, migration, and angiogenesis. When employed for wound, ETN@FeS showed the ability to prevent infection, reduce inflammation, promote angiogenesis, enhance cell proliferation, and remodel keratinocytes. Along with the hemostatic effect, ETN@FeS thus performed comprehensive effects for wound healing in the whole recovery stages. Therefore, our findings provide a multifunctional candidate of ETN and nano-iron sulfide complex which is capable of regulating and promoting wound healing.
伤口愈合需要在包括止血、感染控制、炎症消退、增殖和组织重塑在内的多个程序化阶段进行协调进展。许多纳米材料已显示出促进伤口愈合的巨大潜力，然而，它们中的大多数仅解决了这些过程的部分方面，难以产生足够的效果来实现恢复。在本研究中，我们制备了一种与红细胞模板纳米酶（ETN）整合的纳米硫化铁复合物（ETN@FeS）用于伤口的综合治疗。首先，ETN作为介质在溶剂热反应中限制硫化铁形成FeS纳米复合材料。其次，ETN@FeS通过释放亚铁离子和多硫化物诱导铁死亡样细胞死亡，对耐甲氧西林金黄色葡萄球菌（MRSA）具有杀菌作用。第三，亚铁离子与多硫化物通过抑制NF-κB信号通路的激活发挥抗炎作用，而多硫化物还通过促进血管内皮生长因子A（VEGFA）的激活、启动PI3K/AKT信号通路的磷酸化介导激活来促进血管生成，PI3K/AKT信号通路是控制内皮细胞存活、迁移和血管生成的主要调节级联反应。当用于伤口时，ETN@FeS表现出预防感染、减轻炎症、促进血管生成、增强细胞增殖和重塑角质形成细胞的能力。连同止血作用，ETN@FeS因此在整个恢复阶段对伤口愈合发挥了综合作用。因此，我们的研究结果提供了一种能够调节和促进伤口愈合的ETN和纳米硫化铁复合物的多功能候选物。
