Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College, London, UK.
MRC-PHE Centre for Environment and Health, Analytical & Environmental Sciences Division, Faculty of Life Sciences and Medicine, King's College, London, UK.
Nanomedicine. 2017 Nov;13(8):2517-2521. doi: 10.1016/j.nano.2017.06.008. Epub 2017 Jun 22.
Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLFs). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines. The asthmatic coronal proteome displayed a reduced contribution of surfactant proteins (SP-A and B) and a higher contribution of α1-antitrypsin. Pathway analysis suggested that asthmatic RTLFs may also be deficient in proteins related to metal handling (e.g. lactoferrin). This study demonstrates how the composition of the corona acquired by inhaled nanoparticles is modified in asthma and suggests depressed mucosal immunity even in mild airway disease.
大多数正在开发的吸入式纳米药物用于治疗肺部疾病，但对于它们与呼吸道衬里液（RTLFs）的相互作用却知之甚少。在这里，我们将纳米二氧化硅（作为一种蛋白质浓缩剂）与无标记快照蛋白质组学（LC-MS/MS；通过 ELISA 确认了关键发现）相结合，生成了 RTLF 蛋白质组的定量图谱，并深入了解了演变中的蛋白冠；这些信息将来可能用于通过吸入药物改善药物对肺部的靶向性。哮喘患者的蛋白冠显示表面活性剂蛋白（SP-A 和 B）的贡献减少，而 α1-抗胰蛋白酶的贡献增加。途径分析表明，哮喘 RTFLs 可能还缺乏与金属处理相关的蛋白质（例如乳铁蛋白）。这项研究表明，吸入纳米颗粒获得的蛋白冠的组成在哮喘中是如何被改变的，并表明即使在轻度气道疾病中，粘膜免疫也会受到抑制。
