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.