Hu Qinsheng, Wu Chengcheng, Wang Ling, Cao Dan, Wang Junchao, Du Yangrui, Liu Miao, Li Kaijun
Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
Department of Orthopedic Surgery, Ya'an People's Hospital, Ya'an 625000, China.
J Mater Chem B. 2025 Feb 26;13(9):3067-3079. doi: 10.1039/d4tb02649g.
Osteomyelitis is a serious inflammatory disease mostly caused by bacterial infections. It is necessary to simultaneously eradicate bacterial cells and inhibit inflammation in treating osteomyelitis. Herein, we design an innovative zinc ion (Zn)-based nano delivery system for the management of osteomyelitis. Taking advantage of the coordination self-assembly of Zn, quercetin (QU), and ε-poly-L-lysine (EPL), Zn-containing nanoparticles (denoted as ZQE NPs) are prepared. ZQE NPs are spherical nanoparticles with amorphous structures. They are stable in the physiological neutral environment but can be dissociated in an acidic microenvironment of infection sites. Since Zn is encapsulated into ZQE NPs by coordination interaction, the deactivation of Zn by proteins can be effectively avoided. Therefore, ZQE NPs can maintain excellent bactericidal activity in a protein-rich environment, while dissociative Zn doesn't exhibit obvious bactericidal ability. Meanwhile, ZQE NPs are highly effective at scavenging intracellular reactive oxygen species (ROS) and inhibiting pro-inflammatory cytokines, due to the strong anti-inflammatory effects of QU and Zn. The therapeutic efficacy of ZQE NPs is assessed using a rat model of methicillin-resistant (MRSA)-induced osteomyelitis. Results demonstrate that ZQE NPs effectively eradicate bacterial cells and reduce inflammation , thereby promoting osteogenesis and recovery of osteomyelitis.
骨髓炎是一种主要由细菌感染引起的严重炎症性疾病。在治疗骨髓炎时，有必要同时根除细菌细胞并抑制炎症。在此，我们设计了一种创新的基于锌离子（Zn）的纳米递送系统来治疗骨髓炎。利用Zn、槲皮素（QU）和ε-聚赖氨酸（EPL）的配位自组装，制备了含锌纳米颗粒（记为ZQE NPs）。ZQE NPs是具有无定形结构的球形纳米颗粒。它们在生理中性环境中稳定，但在感染部位的酸性微环境中会解离。由于Zn通过配位相互作用被包裹在ZQE NPs中，可以有效避免蛋白质对Zn的失活作用。因此，ZQE NPs在富含蛋白质的环境中能保持优异的杀菌活性，而游离的Zn则没有明显的杀菌能力。同时，由于QU和Zn具有强大的抗炎作用，ZQE NPs在清除细胞内活性氧（ROS）和抑制促炎细胞因子方面非常有效。使用耐甲氧西林金黄色葡萄球菌（MRSA）诱导的骨髓炎大鼠模型评估ZQE NPs的治疗效果。结果表明，ZQE NPs能有效根除细菌细胞并减轻炎症，从而促进骨髓炎的骨生成和恢复。
