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具有广谱细菌捕获能力的用于血液净化的血液相容性磁性颗粒。

Hemocompatible magnetic particles with broad-spectrum bacteria capture capability for blood purification.

作者信息

Shi Zhenqiang, Jin Lunqiang, He Chao, Li Yupei, Jiang Chunji, Wang Hui, Zhang Jue, Wang Jingxia, Zhao Weifeng, Zhao Changsheng

机构信息

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.

Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China; Institute for Disaster Management and Reconstruction, Sichuan University, Chengdu 610225, China.

出版信息

J Colloid Interface Sci. 2020 Sep 15;576:1-9. doi: 10.1016/j.jcis.2020.04.115. Epub 2020 May 4.

Abstract

Pathogen capture and removal from whole blood is a new strategy for extracorporeal blood purification, especially in initial treatment of sepsis before pathogen identification. Herein, hemocompatible magnetic particles with broad-spectrum bacteria capture capability were proposed for pathogen removal from whole blood, omitting the necessity of pathogen identification. Firstly, we designed and synthesized a new kind of imidazolium-based ionic liquid with good antibacterial activity, and polydopamine coating was utilized as a hemocompatible platform to immobilize ionic liquids on FeO nanoparticles, forming the hemocompatible magnetic particles (FeO@PDA-IL). The magnetic particles exhibited good hemocompatibility and performed well in the removal of various species of clinically significant pathogens from human whole blood, including S. aureus, E. coli, and the hard-to-treat bacteria of P. aeruginosa and Methicillin-resistant S. aureus, which are the most common pathogens in bloodstream infections. Besides, the FeO@PDA-IL particles were also capable to remove bacterial endotoxins from blood, inhibiting further aggravation of sepsis. Overall, we demonstrated the application of hemocompatible magnetic particles in the removal of pathogens and bacterial endotoxins from whole blood via electrostatic and hydrophobic interactions, without significant effects on blood cells or the activation of coagulation and complement, addressing the feasibility of using imidazolium-based ionic liquids for bacteria capture and removal from whole blood. It would contribute to the development of magnetic separation-based approaches to remove bacteria and bacterial endotoxin for extracorporeal blood purification, especially in initial sepsis therapy before pathogen identification.

摘要

从全血中捕获和清除病原体是体外血液净化的一种新策略,特别是在病原体鉴定之前败血症的初始治疗中。在此,我们提出了具有广谱细菌捕获能力的血液相容性磁性颗粒,用于从全血中清除病原体,从而无需进行病原体鉴定。首先,我们设计并合成了一种具有良好抗菌活性的新型咪唑基离子液体,并利用聚多巴胺涂层作为血液相容性平台,将离子液体固定在FeO纳米颗粒上,形成血液相容性磁性颗粒(FeO@PDA-IL)。这些磁性颗粒表现出良好的血液相容性,并且在从人全血中清除各种具有临床意义的病原体方面表现出色,包括金黄色葡萄球菌、大肠杆菌以及血流感染中最常见的难以治疗的铜绿假单胞菌和耐甲氧西林金黄色葡萄球菌。此外,FeO@PDA-IL颗粒还能够从血液中去除细菌内毒素,抑制败血症的进一步加重。总体而言,我们证明了血液相容性磁性颗粒通过静电和疏水相互作用从全血中清除病原体和细菌内毒素的应用,对血细胞或凝血及补体激活没有显著影响,解决了使用咪唑基离子液体从全血中捕获和清除细菌的可行性。这将有助于开发基于磁分离的方法来去除细菌和细菌内毒素用于体外血液净化,特别是在病原体鉴定之前的初始败血症治疗中。

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