Lv Hui, Yang Ming, Yang Yusheng, Tang Zhenzhen, Guo Yuan, Zhou Jiangling, Gui Yingtao, Huang Rong, Cai Juan, Yu Bo, Yang Jing, Bao Ying, Zhang Zhongrong, Zhang Dinglin, Hou Tianyong
Department of Emergency and trauma orthopedics, the 958th Hospital of Chinese People's Liberation Army, Army Medical University (Third Military Medical University), Chongqing 400023, China.
Department of Chemistry, College of Basic Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China.
ACS Nano. 2025 Feb 11;19(5):5253-5268. doi: 10.1021/acsnano.4c11956. Epub 2025 Jan 31.
Methicillin-resistant (MRSA) causes osteomyelitis (OM), which seriously threatens public health due to its antimicrobial resistance. To increase the sensitivity of antibiotics and eradicate intracellular bacteria, a Zn and vancomycin (Van) codelivered nanotherapeutic (named Man-Zn/Van NPs) was fabricated and characterized via mannose (Man) modification. Man-Zn/Van NPs exhibit significant inhibitory activity against extra- and intracellular MRSA and obviously decrease the minimum inhibitory concentration of Van. Man-Zn/Van NPs can be easily internalized by MRSA-infected macrophages and significantly accumulated in infected bone via Man-mediated targeting. In vivo experiments in a mouse OM model verified that Man-Zn/Van NPs significantly reduce the extra- and intracellular MRSA burden, improve gait patterns, increase bone mass, and decrease inflammatory cytokine expression. The antibacterial mechanism of Man-Zn/Van NPs includes destruction of the MRSA membrane, degeneration of intracellular proteins and DNA, inhibition of MRSA glycolysis, and intervention in the energy metabolism of bacteria. Overall, this metal-antibiotic nanotherapeutics strategy provides new insight for combating extra- and intracellular infections caused by MRSA-induced OM.
耐甲氧西林金黄色葡萄球菌（MRSA）可引发骨髓炎（OM），因其抗菌耐药性而严重威胁公众健康。为提高抗生素敏感性并根除细胞内细菌，通过甘露糖（Man）修饰制备并表征了一种共递送锌和万古霉素（Van）的纳米治疗剂（命名为Man-Zn/Van NPs）。Man-Zn/Van NPs对细胞外和细胞内的MRSA均表现出显著的抑制活性，并明显降低了Van的最低抑菌浓度。Man-Zn/Van NPs能够被MRSA感染巨噬细胞轻易内化，并通过Man介导的靶向作用在感染骨中显著蓄积。在小鼠OM模型中的体内实验证实，Man-Zn/Van NPs可显著减轻细胞外和细胞内MRSA负荷，改善步态模式，增加骨量，并降低炎性细胞因子表达。Man-Zn/Van NPs的抗菌机制包括破坏MRSA细胞膜、使细胞内蛋白质和DNA变性、抑制MRSA糖酵解以及干预细菌的能量代谢。总体而言，这种金属-抗生素纳米治疗策略为对抗由MRSA引起的OM所导致的细胞外和细胞内感染提供了新的见解。
