Leveraging nanoparticle protein corona to advance plasma proteome profiling

The blood plasma proteome is a rich reservoir of potential biomarkers, yet its analysis is hindered by a protein concentration dynamic range exceeding ten orders of magnitude. Traditional fractionation and enrichment methods often present limitations in detecting rare proteins masked by the presence of abundant proteins. A promising frontier technology has emerged to overcome such limitations: leveraging nanoparticle protein coronas to enrich low-abundance plasma proteins and unveil previously inaccessible layers of the proteome. This Perspective highlights the capabilities of the protein corona technology in enhancing proteome coverage, addresses its current limitations and outlines future directions in proteoform analysis and causal inference. Proteomics has long suffered from artifacts and effects due to the wide range of protein concentrations. Here, the authors offer a perspective on the use of nanoparticles to enhance the detection of low-abundance proteins by using the formation of the protein corona.