Nanomedicine Lab, Faculty of Biology, Medicine & Health, AV Hill Building, The University of Manchester, Manchester, M13 9PT, UK.
Nanoscale. 2020 May 14;12(18):10240-10253. doi: 10.1039/d0nr02788j.
Rapid and accurate diagnosis of sepsis remains clinically challenging. The lack of specific biomarkers that can differentiate sepsis from non-infectious systemic inflammatory diseases often leads to excessive antibiotic treatment. Novel diagnostic tests are urgently needed to rapidly and accurately diagnose sepsis and enable effective treatment. Despite investment in cutting-edge technologies available today, the discovery of disease-specific biomarkers in blood remains extremely difficult. The highly dynamic environment of plasma restricts access to vital diagnostic information that can be obtained by proteomic analysis. Here, we employed clinically used lipid-based nanoparticles (AmBisome®) as an enrichment platform to analyze the human plasma proteome in the setting of sepsis. We exploited the spontaneous interaction of plasma proteins with nanoparticles (NPs) once in contact, called the 'protein corona', to discover previously unknown disease-specific biomarkers for sepsis diagnosis. Plasma samples obtained from non-infectious acute systemic inflammation controls and sepsis patients were incubated ex vivo with AmBisome® liposomes, and the resultant protein coronas were thoroughly characterised and compared by mass spectrometry (MS)-based proteomics. Our results demonstrate that the proposed nanoparticle enrichment technology enabled the discovery of 67 potential biomarker proteins that could reproducibly differentiate non-infectious acute systemic inflammation from sepsis. This study provides proof-of-concept evidence that nanoscale-based 'omics' enrichment technologies have the potential to substantially improve plasma proteomics analysis and to uncover novel biomarkers in a challenging clinical setting.
快速准确地诊断脓毒症仍然具有临床挑战性。缺乏能够将脓毒症与非感染性全身炎症性疾病区分开来的特异性生物标志物，这往往导致过度使用抗生素治疗。迫切需要新的诊断测试来快速准确地诊断脓毒症，并实现有效治疗。尽管目前投资了先进的技术，但在血液中发现疾病特异性生物标志物仍然极其困难。血浆的高度动态环境限制了对通过蛋白质组学分析可以获得的重要诊断信息的访问。在这里，我们采用临床使用的基于脂质的纳米颗粒（AmBisome®）作为富集平台，在脓毒症的背景下分析人类血浆蛋白质组。我们利用纳米颗粒（NPs）与血浆蛋白一旦接触就会自发相互作用，称为“蛋白质冠”，来发现以前未知的用于脓毒症诊断的疾病特异性生物标志物。从非感染性急性全身炎症对照和脓毒症患者获得的血浆样本在体外用 AmBisome®脂质体孵育，并用基于质谱（MS）的蛋白质组学对所得蛋白质冠进行彻底表征和比较。我们的结果表明，所提出的纳米颗粒富集技术能够发现 67 种潜在的生物标志物蛋白，这些蛋白可以重复区分非感染性急性全身炎症和脓毒症。这项研究提供了概念验证证据，表明基于纳米尺度的“组学”富集技术有可能极大地改善血浆蛋白质组学分析，并在具有挑战性的临床环境中发现新的生物标志物。
