南湖新闻网讯（通讯员 任梅渗）狂犬病是狂犬病毒引起的致死性人兽共患病。该病分布于全球150余个国家，每年造成6万人以上的死亡，一旦发病后死亡率接近100%，目前尚无有效的临床治疗手段。我校农业微生物学国家重点实验室赵凌教授团队联合理学院韩鹤友教授开发了一种基于新型纳米材料的光热治疗方法，并在狂犬病小鼠模型上获得了良好的治疗效果，为临床治疗狂犬病毒及其他嗜神经病毒感染提供了有效策略。

在该研究中，赵凌教授团队首先筛选了一个能够特异性结合狂犬病毒表面糖蛋白的适配体，并将该适配体结合在一个外形和大小接近狂犬病毒的纳米金棒表面。该金纳米棒在静脉注射后能够有效穿越小鼠血脑屏障入脑，并且靶向性结合于狂犬病毒感染的神经细胞。利用近红外光照射感染小鼠的脑部后，可以在纳米金棒表面产生局部高温，“烧死”感染病毒的细胞，最终清除脑内的病毒，该方法称之为“光热疗法”。

研究人员分别在感染狂犬病毒后的第3天、第6天和第9天对小鼠进行了每次5分钟的光热疗法，结果显示治疗组中有60%小鼠能够存活，并且在21天之后恢复到正常小鼠的健康水平，而未治疗组小鼠在感染病毒后8至12天内全部死亡。在小鼠模型上，该光热疗法展现了良好的治疗效果，为后续临床治疗狂犬病提供了新思路。

基于纳米金棒的光热疗法在小鼠模型上治疗狂犬病的示意图

本研究是赵凌教授加入我校交叉科学研究院后利用纳米材料精准检测狂犬病毒（Analytical Chemistry, 2020）之后，在动物病毒-纳米材料交叉学科领域取得的又一阶段性成果。上述研究得到国家重点研发计划和国家自然科学基金等经费的大力支持。

审核人：赵凌

【英文摘要】

The infection of the neurotropic virus damages the central nervous system (CNS) and often leads to humans' fatal symptoms. Rabies is a lethal disease caused by a typical neurotropic virus, rabies virus (RABV). To date, there is no effective clinical therapy for rabies. In this report, an aptamer conjugated RVG-Apt-PEG-Silica gold nanorods (AuNR)-based photothermal therapy (PTT) was developed and evaluated in a mouse model. The DNA aptamer was conjugated on the nanoparticle to provide specificity for targeting RABV glycoprotein in cells and mouse brains. A 29-aa rabies virus glycopeptide (RVG) was conjugated on the nanoparticle to enhance CNS delivery. The virions were inactivated in cell supernatant, and an approximately 100-fold decrease of viral load was observed in cells 5min post-PTT. This AuNR did not cause distinct apoptosis, inflammation, or pathological lesion in the mouse brains post PTT. At 3day post-infection, significantly enhanced survival ratio (60%) was observed in mice received PTT compared with the mice without PTT. In the PTT group, both the viral RNA level and the distribution of RABV in mouse brains were significantly decreased. Collectively, aptamer conjugated RVG-Apt-PEG-Silica AuNR-based PTT could be considered as a promising strategy for clinical treatment with neurotropic virus infection.

论文链接： https://authors.elsevier.com/a/1cSoQ_VWlWGGyy