Rapid, Deep and Precise Profiling of the Plasma Proteome with Multi-Nanoparticle Protein Corona

We report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for large-scale, efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples. Spike experiments confirmed a linear signal response. The median coefficient of variation was ~22%. The NP corona formation enables deep sampling of the plasma proteome. We screened 43 NPs and selected a panel of 5, which detected more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise relative quantification based on unique interactions between proteins and a panel of engineered NPs for deep and scalable quantitative proteomic studies and biomarker discovery.