Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung.
Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung.
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DOI：
10.2147/ijn.s39888
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发表时间：
2013
影响因子：
8
通讯作者：
Voelker DR
中科院分区：
文献类型：
--
作者：
Numata M;Grinkova YV;Mitchell JR;Chu HW;Sligar SG;Voelker DR
人们对应用纳米技术解决药物治疗性给药的难题越来越感兴趣。纳米盘由被两亲性膜支架蛋白包围的稳定的盘状脂质双层组成，所述两亲性膜支架蛋白是高密度脂蛋白的人Apo A-I组分的工程化变体，纳米盘已经是用于在颗粒中提供受控脂质组成的成功平台，所述颗粒特别用于研究膜蛋白结构和功能。在这篇文章中，我们证明了纳米盘在体外和体内与次要肺表面活性剂磷脂棕榈酰油酰磷脂酰甘油（POPG）自组装时，可有效抑制呼吸道合胞病毒（RSV）感染。含有POPG（nPOPG）的纳米盘制剂拮抗RSV感染激发的Beas 2B上皮细胞产生白细胞介素-8，IC 50为19.3 μg/mL。在定量体外空斑试验中，nPOPG使RSV感染降低了93%。在体内，nPOPG抑制炎性细胞浸润到肺中，以及响应于RSV攻击的IFN-γ产生。nPOPG还完全抑制RSV引起的肺组织的组织病理学变化，并使从肺组织回收的病毒量减少96%。根据人Apo A-I组分回收率的定量，估计nPOPG的转换率半衰期为60-120分钟（m）。从这些数据中，我们得出结论，nPOPG是一种有效的拮抗剂RSV感染及其炎症后遗症在体外和体内。
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.