Wang Mengtian, Liu Yangkun, Yang Shuqing, Wang Xuanbing, Duan Qindan, Liu Jiankai, Tan Xudong, Long Linjing, Liu Siyi, Xiao Yawen, Li Zhao, Han Changhao, Yi Yaoxing, Zhang Yuchan, Wang Guixue, Zang Guangchao
The Second Affiliated Hospital of Chongqing Medical University International Medical College of Chongqing Medical University, Laboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, 1, Medical College Road, Yuzhong District, Chongqing, 400016, China.
School of Medical Technology, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081, China.
Adv Healthc Mater. 2025 Feb;14(4):e2402579. doi: 10.1002/adhm.202402579. Epub 2024 Oct 21.
The rational utilization of ROS is key to treating infected wounds. Exogenous ROS can destroy bacterial structures, quickly kill bacteria, and inhibit secondary infections. However, excess ROS at the wound will cause a secondary inflammatory response. Acute infections exacerbate this damage by increasing endogenous ROS, complicating the maintenance of ROS homeostasis. Therefore, regulating the balance of ROS production and scavenging in wounds has emerged as a promising strategy for wound treatment. Conventional ROS balancing platforms are mostly based on the " all for one" strategy of functional superposition and lack self-adaptability and integration. To subvert this conventional strategy, this study proposes a "one for all" self-adaptive integrated photodynamic therapy (PDT)-antioxidant model to actively regulate the ROS balance. A gelatin-hyaluronic acid hydrogel embedded with Se-modified cerium dioxide nanoparticles (Gel-HA-Se@CeO NPs) is designed for treating infected wounds. The Se@CeO NPs serve both as nanoenzymes and photosensitizers(PS). As nanoenzymes, they exhibit catalase and superoxide dismutase activities, converting hydrogen peroxide and superoxide anions into oxygen. As a PS, it synergizes with oxygen under NIR irradiation to rapidly produce singlet oxygen. Additionally, Se modification enhances the PDT effects by disrupting bacterial antioxidant systems. In vitro and in vivo experiments revealed that the ROS balance platform polarizes M1-type macrophages to M2-type macrophages, altering the wound microenvironment from proinflammatory to prohealing. RNA sequencing revealed that this hydrogel accelerated the reconstruction of the vascular network of the wound by activating the PI3K/AKT pathway and increasing VEGF secretion.This strategy is believed to be beneficial not only for infected wounds but also for treating other conditions that involve the regulation of reactive oxygen species, such as tumors and bacterial infections.
活性氧（ROS）的合理利用是治疗感染伤口的关键。外源性ROS可破坏细菌结构，快速杀灭细菌并抑制继发性感染。然而，伤口处过量的ROS会引发继发性炎症反应。急性感染通过增加内源性ROS加剧这种损伤，使ROS稳态的维持变得复杂。因此，调节伤口中ROS产生与清除的平衡已成为一种有前景的伤口治疗策略。传统的ROS平衡平台大多基于功能叠加的“全为一”策略，缺乏自适应性和整合性。为了颠覆这种传统策略，本研究提出了一种“一为全”的自适应集成光动力疗法（PDT）-抗氧化剂模型，以主动调节ROS平衡。设计了一种嵌入硒改性二氧化铈纳米颗粒（Gel-HA-Se@CeO NPs）的明胶-透明质酸水凝胶用于治疗感染伤口。Se@CeO NPs既作为纳米酶又作为光敏剂（PS）。作为纳米酶，它们表现出过氧化氢酶和超氧化物歧化酶活性，将过氧化氢和超氧阴离子转化为氧气。作为PS，它在近红外照射下与氧气协同作用，快速产生单线态氧。此外，硒改性通过破坏细菌抗氧化系统增强了PDT效果。体外和体内实验表明，ROS平衡平台将M1型巨噬细胞极化为M2型巨噬细胞，将伤口微环境从促炎状态转变为促愈合状态。RNA测序显示，这种水凝胶通过激活PI3K/AKT途径和增加VEGF分泌，加速了伤口血管网络的重建。这种策略不仅被认为对感染伤口有益，而且对治疗其他涉及活性氧调节的病症，如肿瘤和细菌感染也有益。
