Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO, USA.
Int J Nanomedicine. 2013;8:1417-27. doi: 10.2147/IJN.S39888. Epub 2013 Apr 15.
There is increasing interest in the application of nanotechnology to solve the difficult problem of therapeutic administration of pharmaceuticals. Nanodiscs, composed of a stable discoidal lipid bilayer encircled by an amphipathic membrane scaffold protein that is an engineered variant of the human Apo A-I constituent of high-density lipoproteins, have been a successful platform for providing a controlled lipid composition in particles that are especially useful for investigating membrane protein structure and function. In this communication, we demonstrate that nanodiscs are effective in suppressing respiratory syncytial viral (RSV) infection both in vitro and in vivo when self-assembled with the minor pulmonary surfactant phospholipid palmitoyloleoylphosphatidylglycerol (POPG). Preparations of nanodiscs containing POPG (nPOPG) antagonized interleukin-8 production from Beas2B epithelial cells challenged by RSV infection, with an IC50 of 19.3 μg/mL. In quantitative in vitro plaque assays, nPOPG reduced RSV infection by 93%. In vivo, nPOPG suppressed inflammatory cell infiltration into the lung, as well as IFN-γ production in response to RSV challenge. nPOPG also completely suppressed the histopathological changes in lung tissue elicited by RSV and reduced the amount of virus recovered from lung tissue by 96%. The turnover rate of nPOPG was estimated to have a halftime of 60-120 minutes (m), based upon quantification of the recovery of the human Apo A-I constituent. From these data, we conclude that nPOPG is a potent antagonist of RSV infection and its inflammatory sequelae both in vitro and in vivo.
人们越来越关注纳米技术在解决药物治疗管理难题中的应用。纳米盘由一个稳定的盘状脂质双层组成，周围环绕着一种两亲性膜支架蛋白，这种蛋白是高密度脂蛋白中载脂蛋白 A-I 成分的工程变体，是提供具有可控脂质组成的颗粒的成功平台，特别有助于研究膜蛋白结构和功能。在本通讯中，我们证明当与肺部表面活性剂磷脂棕榈酰油酰磷脂酰甘油（POPG）自组装时，纳米盘可有效抑制呼吸道合胞病毒（RSV）在体外和体内的感染。含有 POPG 的纳米盘制剂（nPOPG）拮抗 RSV 感染后 Beas2B 上皮细胞产生白细胞介素-8，IC50 为 19.3μg/ml。在定量体外噬菌斑测定中，nPOPG 使 RSV 感染减少了 93%。在体内，nPOPG 抑制了炎症细胞浸润到肺部，以及 IFN-γ 对 RSV 挑战的产生。nPOPG 还完全抑制了 RSV 引起的肺组织组织病理学变化，并使从肺组织中回收的病毒量减少了 96%。根据对人载脂蛋白 A-I 成分回收的定量，nPOPG 的半衰期估计为 60-120 分钟（m）。根据这些数据，我们得出结论，nPOPG 是 RSV 感染及其炎症后遗症的有效拮抗剂，无论是在体外还是体内。
