Wang Qi, Luo Zheng, Li Zhiguo, Hu Haohua, Lin Yuting, Fan Xiaotong, Li Zibiao, Wu Yun-Long
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, PR China.
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, PR China; Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis #08-03, Singapore, 138634, Republic of Singapore.
Acta Biomater. 2025 Jan 24;193:334-347. doi: 10.1016/j.actbio.2024.12.044. Epub 2024 Dec 18.
Hypoxia, high ROS levels and chronic inflammation are the main factors that hinder the healing of diabetic wounds. Long-term exposed wounds are prone to bacterial infection, especially MRSA infection, which exacerbates the complex wound microenvironment of diabetes and threatens patients' lives. Here, we developed a ROS nanopurifier (CSVNP), which was prepared by loading superoxide dismutase (SOD), catalase (CAT) and vancomycin into nanogels through in-situ polymerization. CSVNP can effectively increase enzyme loading and stability, and improve cascade reaction efficiency between enzymes through nanosize effect, so that CSVNP can use a variety of ROS (HO and ·O) as oxygen sources to generate much oxygen in situ, which can effectively alleviate the hypoxic environment and inflammatory response of diabetic tissues, theraby promoting cell migration and angiogenesis, and accelerating wound healing. In addition, the generated oxygen can further promote the transformation of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages and reduce pro-inflammatory factors (TNF-α, IL-6, and IL-1β) release. CSVNP can also effectively eradicate MRSA by releasing vancomycin, preventing bacterial infection from exacerbating the deterioration of diabetic wounds. This multifunctional ROS nanopurifier with antiphlogosis, antibacterial and in-situ oxygen supply, provides a new strategy with universal and translational prospects for clinical diabetic tissue damage. STATEMENT OF SIGNIFICANCE: Methicillin-resistant staphylococcus aureus (MRSA)-infected diabetic wounds face significant challenges in clinical care, characterized by high ROS levels, acute inflammation, vascular lesions, and hypoxia, which impede healing and risk severe complications. Here, we originally developed a reactive oxygen species (ROS) nanopurifier prepared by in-situ polymerization of superoxide dismutase (SOD), catalase (CAT), and vancomycin. It uses SOD and CAT to continuously convert ROS (HO and ·O) into O in diabetic tissues, effectively improving hypoxia and chronic inflammation, thereby promoting angiogenesis and cell proliferation and migration, and accelerating diabetic wound healing. Vancomycin can effectively kill MRSA bacteria, avoid bacterial infection spread, and reduce complications risk. This safe, efficient and easy-to-prepare ROS nanopurifier provides a general strategy for repairing MRSA-infected diabetic tissue damage.
缺氧、高活性氧水平和慢性炎症是阻碍糖尿病伤口愈合的主要因素。长期暴露的伤口容易发生细菌感染，尤其是耐甲氧西林金黄色葡萄球菌（MRSA）感染，这会加剧糖尿病复杂的伤口微环境并威胁患者生命。在此，我们开发了一种活性氧纳米净化器（CSVNP），它是通过原位聚合将超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和万古霉素负载到纳米凝胶中制备而成。CSVNP能有效提高酶负载量和稳定性，并通过纳米尺寸效应提高酶之间的级联反应效率，使CSVNP能够利用多种活性氧（HO和·O）作为氧源原位产生大量氧气，有效缓解糖尿病组织的缺氧环境和炎症反应，从而促进细胞迁移和血管生成，加速伤口愈合。此外，产生的氧气可进一步促进促炎性M1巨噬细胞向抗炎性M2巨噬细胞转化，并减少促炎因子（TNF-α、IL-6和IL-1β）的释放。CSVNP还可通过释放万古霉素有效根除MRSA，防止细菌感染加剧糖尿病伤口的恶化。这种具有抗炎、抗菌和原位供氧功能的多功能活性氧纳米净化器，为临床糖尿病组织损伤提供了一种具有普遍应用和转化前景的新策略。重要意义声明：耐甲氧西林金黄色葡萄球菌（MRSA）感染的糖尿病伤口在临床护理上面临重大挑战，其特征为高活性氧水平、急性炎症、血管病变和缺氧，这些因素阻碍愈合并存在严重并发症风险。在此，我们首次开发了一种通过超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和万古霉素原位聚合制备的活性氧（ROS）纳米净化器。它利用SOD和CAT在糖尿病组织中持续将活性氧（HO和·O）转化为O，有效改善缺氧和慢性炎症，从而促进血管生成以及细胞增殖和迁移，加速糖尿病伤口愈合。万古霉素可有效杀灭MRSA细菌，避免细菌感染扩散，降低并发症风险。这种安全、高效且易于制备的ROS纳米净化器为修复MRSA感染的糖尿病组织损伤提供了一种通用策略。
