Metal Ion and Antibiotic Co-loaded Nanoparticles for Combating Methicillin-Rresistant Staphylococcus aureus-Induced Osteomyelitis.

IF 16 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY ACS Nano Pub Date : 2025-02-11 Epub Date: 2025-01-31 DOI:10.1021/acsnano.4c11956

Hui Lv, Ming Yang, Yusheng Yang, Zhenzhen Tang, Yuan Guo, Jiangling Zhou, Yingtao Gui, Rong Huang, Juan Cai, Bo Yu, Jing Yang, Ying Bao, Zhongrong Zhang, Dinglin Zhang, Tianyong Hou

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Abstract

Methicillin-resistant Staphylococcus aureus (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 Zn²⁺ and vancomycin (Van) codelivered nanotherapeutic (named Man-Zn²⁺/Van NPs) was fabricated and characterized via mannose (Man) modification. Man-Zn²⁺/Van NPs exhibit significant inhibitory activity against extra- and intracellular MRSA and obviously decrease the minimum inhibitory concentration of Van. Man-Zn²⁺/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-Zn²⁺/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-Zn²⁺/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.

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金属离子和抗生素共载纳米颗粒对抗耐甲氧西林- r金黄色葡萄球菌诱导的骨髓炎。

耐甲氧西林金黄色葡萄球菌（MRSA）引起骨髓炎（OM），严重威胁公众健康。为了提高抗生素的敏感性和根除细胞内细菌，制备了一种Zn2+和万古霉素（Van）共递送的纳米治疗剂（Man -Zn2+/Van NPs），并通过甘露糖（Man）修饰对其进行了表征。Man-Zn2+/Van NPs对细胞外和细胞内MRSA具有显著的抑制活性，并明显降低了Van的最低抑制浓度。Man-Zn2+/Van NPs可以很容易地被mrsa感染的巨噬细胞内化，并通过人介导的靶向在感染的骨中显著积累。小鼠OM模型的体内实验证实，Man-Zn2+/Van NPs可显著降低细胞外和细胞内MRSA负担，改善步态模式，增加骨量，降低炎症细胞因子表达。Man-Zn2+/Van NPs的抗菌机制包括破坏MRSA膜，使细胞内蛋白和DNA变性，抑制MRSA糖酵解，干预细菌的能量代谢。总的来说，这种金属-抗生素纳米治疗策略为对抗mrsa诱导的OM引起的细胞外和细胞内感染提供了新的见解。

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来源期刊

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.