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近红外光敏感型纳米神经免疫阻断胶囊缓解疼痛并增强坏死性感染的固有免疫反应。

Near-Infrared Light-Sensitive Nano Neuro-Immune Blocker Capsule Relieves Pain and Enhances the Innate Immune Response for Necrotizing Infection.

机构信息

State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology , Wuhan University , Wuhan 430079 , China.

Institute of Health and Biomedical Innovation , Queensland University of Technology , Kelvin Grove , Queensland 4059 , Australia.

出版信息

Nano Lett. 2019 Sep 11;19(9):5904-5914. doi: 10.1021/acs.nanolett.9b01459. Epub 2019 Aug 9.

Abstract

Sensory neurons promote profound suppressive effects on neutrophils during infection and contribute to the pathogenesis of necrotizing infection ("flesh-eating disease"). Thus, the development of new antibacterial agents for necrotizing infection is promising because of the clear streptococcal neuro-immune communication. Herein, based on the immune escape membrane exterior and competitive membrane functions of the glioma cell membrane, a novel nano neuro-immune blocker capsule was designed to prevent neuronal activation and improve neutrophil immune responses for necrotizing infection. These nano neuro-immune blockers could neutralize streptolysin S, suppress neuron pain conduction and calcitonin gene-related peptide release, and recruit neutrophils to the infection site, providing a strong therapeutic effect against necrotizing infection. Furthermore, nano neuro-immune blockers could serve as an effective inflammatory regulator and antibacterial agent via photothermal effects under near-infrared irradiation. In the -induced necrotizing fasciitis mouse model, nano neuro-immune blockers showed significant therapeutic efficacy by ameliorating sensitivity to pain and promoting the antibacterial effect of neutrophils.

摘要

感觉神经元在感染过程中对中性粒细胞产生深远的抑制作用,并有助于坏死性感染(“食肉病”)的发病机制。因此,由于明确的链球菌神经免疫通讯,开发新型抗坏死性感染的抗菌药物具有广阔的前景。在此基础上,基于神经胶质瘤细胞膜的免疫逃逸膜外和竞争膜功能,设计了一种新型纳米神经免疫阻断胶囊,以防止神经元激活并改善中性粒细胞对坏死性感染的免疫反应。这些纳米神经免疫阻断剂可以中和链球菌溶血素 S,抑制神经元疼痛传导和降钙素基因相关肽释放,并将中性粒细胞募集到感染部位,对坏死性感染具有强大的治疗作用。此外,纳米神经免疫阻断剂在近红外辐射下还可以通过光热效应作为有效的炎症调节剂和抗菌剂。在-诱导的坏死性筋膜炎小鼠模型中,纳米神经免疫阻断剂通过改善疼痛敏感性和促进中性粒细胞的抗菌作用显示出显著的治疗效果。

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