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Bacterial Outer Membrane-Based Biomimetic Immune Adaptors: Mild Immunomodulatory and Bacterial Targeted Delivery Strategy Against Implant-Related Infections
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-06-19 , DOI: 10.1002/adfm.202304168
Cheng Ding 1 , Renke He 1 , Tao Cheng 1 , Jinxia Wang 2 , Xijian Liu 2 , Geyong Guo 1 , Yunfeng Chen 1
Affiliation  

Implant-related infections (IRIs) are difficult to manage and are a major cause of surgical failure. The formation of biofilms with a solid barrier on the surface of implants and concomitant suppression of the local immune response constitute major challenges for treating IRIs. This study develops a multifunctional biomimetic immune adaptor (Hybrid Membrane@Levo@SiO2; HMLS) generated by loading the antibiotic levofloxacin (Levo) into silica nanoparticles and coating the particles with a hybrid membrane formed from outer membrane vesicles (OMVs) of Escherichia coli and red blood cell membranes (RBCMs). The HMLS nanoplatform is designed to address the challenges associated with IRIs through a dual-approach strategy. First, the unique immunogenicity of OMVs regulates the antibacterial immune responses of innate immune cells and reverses the immunosuppressive microenvironment around IRIs. Second, the homotypic targeting effect of OMVs in the hybrid membrane provides HMLS with bacterial targeting functions and efficient bactericidal effects. Additionally, the RBCMs endow the hybrid membrane with mild immunogenicity, which prevents excessive inflammatory stimulation. The synergistic strategy of HMLS exhibits superior antibiofilm effects both in vivo and in vitro, providing a new option for the clinical treatment of refractory IRIs.

中文翻译:

基于细菌外膜的仿生免疫适配器:针对植入物相关感染的轻度免疫调节和细菌靶向递送策略

种植体相关感染(IRIs)难以处理,是手术失败的主要原因。在植入物表面形成具有坚固屏障的生物膜以及随之而来的局部免疫反应的抑制构成了治疗 IRI 的主要挑战。本研究开发了一种多功能仿生免疫适配器(Hybrid Membrane@Levo@SiO 2 ; HMLS),其通过将抗生素左氧氟沙星(Levo)负载到二氧化硅纳米颗粒中并用由大肠杆菌外膜囊泡(OMV)形成的混合膜涂覆颗粒而产生和红细胞膜(RBCM)。HMLS 纳米平台旨在通过双方法策略解决与 IRI 相关的挑战。首先,OMV 独特的免疫原性调节先天免疫细胞的抗菌免疫反应,并逆转 IRI 周围的免疫抑制微环境。其次,杂化膜中OMV的同型靶向作用为HMLS提供了细菌靶向功能和高效的杀菌作用。此外,RBCM赋予混合膜温和的免疫原性,防止过度的炎症刺激。HMLS的协同策略在体内和体外均表现出优异的抗生物膜作用,为难治性IRIs的临床治疗提供了新的选择。
更新日期:2023-06-19
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