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

TLDR

Large‑scale, unbiased proteomics are limited by the plasma proteome’s complexity, and protein coronas form when nanoparticles contact biofluids. The study introduces a highly parallel protein quantitation platform that integrates nanoparticle protein coronas with liquid chromatography‑mass spectrometry to enable efficient proteomic profiling. By varying engineered nanoparticles’ physicochemical properties, distinct protein corona patterns are generated, allowing differential and reproducible interrogation of biological samples, including deep plasma proteome sampling, within the integrated LC‑MS platform. Spike experiments confirmed a linear signal response with a median coefficient of variation of 22 %, and screening 43 nanoparticles led to a panel of five that detected over 2,000 proteins from 141 plasma samples in a 96‑well automated workflow, demonstrating deep coverage, high throughput, and precise quantification in a pilot non‑small cell lung cancer classification study.

Abstract

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.