Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona

• Published in: Nature communications Vol. 11; no. 1; pp. 3662 - 14
• Main Authors: Blume, John E., Manning, William C., Troiano, Gregory, Hornburg, Daniel, Figa, Michael, Hesterberg, Lyndal, Platt, Theodore L., Zhao, Xiaoyan, Cuaresma, Rea A., Everley, Patrick A., Ko, Marwin, Liou, Hope, Mahoney, Max, Ferdosi, Shadi, Elgierari, Eltaher M., Stolarczyk, Craig, Tangeysh, Behzad, Xia, Hongwei, Benz, Ryan, Siddiqui, Asim, Carr, Steven A., Ma, Philip, Langer, Robert, Farias, Vivek, Farokhzad, Omid C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.07.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 49/47; 631/1647/296; 631/45/612/1221; 631/61/475; 631/67/1612/1350; 639/925/350/354; 82/58; Adult; Aged; Aged, 80 and over; Automatic pilots; Biological properties; Biological samples; Biomarkers; Blood Proteins - analysis; Blood Proteins - chemistry; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - diagnosis; Chromatography, High Pressure Liquid - methods; Coefficient of variation; Complexity; Coronas; Depth profiling; Diagnosis, Differential; Female; Healthy Volunteers; Humanities and Social Sciences; Humans; Interrogation; Liquid chromatography; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Male; Mass spectrometry; Mass spectroscopy; Middle Aged; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Non-small cell lung carcinoma; Physicochemical properties; Pilot Projects; Plasma; Protein Corona - analysis; Protein Corona - chemistry; Proteins; Proteomes; Proteomics; Proteomics - methods; Quantitation; Reproducibility of Results; Sampling; Science; Science (multidisciplinary); Small cell lung carcinoma; Tandem Mass Spectrometry - methods; Time Factors; Workflow
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17033-7

Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for 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, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise quantification based on unique interactions between proteins and NPs engineered for deep and scalable quantitative proteomic studies. Large-scale, unbiased proteomics studies of biological samples like plasma are constrained by the complexity of the proteome. Herein, the authors develop a highly parallel protein quantitation platform leveraging multi nanoparticle protein coronas for deep proteome sampling and biomarker discovery.