Mass Spectrometry-Based Top-Down Proteomics in Nanomedicine: Proteoform-Specific Measurement of Protein Corona

Overview

Journal ACS Nano

Publisher American Chemical Society

Specialty Biotechnology

Date 2024 Sep 14

PMID 39276099

Authors

Seyed Amirhossein Sadeghi

Ali Akbar Ashkarran

Qianyi Wang

Guijie Zhu

Morteza Mahmoudi

Liangliang Sun

Affiliations

Soon will be listed here.

Abstract

Conventional mass spectrometry (MS)-based bottom-up proteomics (BUP) analysis of the protein corona [i.e., an evolving layer of biomolecules, mostly proteins, formed on the surface of nanoparticles (NPs) during their interactions with biomolecular fluids] enabled the nanomedicine community to partly identify the biological identity of NPs. Such an approach, however, fails to pinpoint the specific proteoforms─distinct molecular variants of proteins in the protein corona. The proteoform-level information could potentially advance the prediction of the biological fate and pharmacokinetics of nanomedicines. Recognizing this limitation, this study pioneers a robust and reproducible MS-based top-down proteomics (TDP) technique for characterizing proteoforms in the protein corona. Our TDP approach has successfully identified about 900 proteoforms in the protein corona of polystyrene NPs, ranging from 2 to 70 kDa, revealing proteoforms of 48 protein biomarkers with combinations of post-translational modifications, signal peptide cleavages, and/or truncations─details that BUP could not fully discern. This advancement in MS-based TDP offers a more advanced approach to characterize NP protein coronas, deepening our understanding of NPs' biological identities. We, therefore, propose using both TDP and BUP strategies to obtain more comprehensive information about the protein corona, which, in turn, can further enhance the diagnostic and therapeutic efficacy of nanomedicine technologies.

Citing Articles

Small molecule modulation of protein corona for deep plasma proteome profiling.

Ashkarran A, Gharibi H, Sadeghi S, Modaresi S, Wang Q, Lin T Nat Commun. 2024; 15(1):9638.

PMID: 39511193 PMC: 11544298. DOI: 10.1038/s41467-024-53966-z.

Deep Profiling of Plasma Proteoforms with Engineered Nanoparticles for Top-Down Proteomics.

Huang C, Hollas M, Sanchez A, Bhattacharya M, Ho G, Sundaresan A J Proteome Res. 2024; 23(10):4694-4703.

PMID: 39312774 PMC: 11789057. DOI: 10.1021/acs.jproteome.4c00621.

Mass Spectrometry-Based Top-Down Proteomics in Nanomedicine: Proteoform-Specific Measurement of Protein Corona.

Sadeghi S, Ashkarran A, Wang Q, Zhu G, Mahmoudi M, Sun L ACS Nano. 2024; .

PMID: 39276099 PMC: 11440641. DOI: 10.1021/acsnano.4c04675.

The role of protein corona in advancing plasma proteomics.

Saei A, Sun L, Mahmoudi M Proteomics. 2024; 25(1-2):e2400028.

PMID: 39221533 PMC: 11735278. DOI: 10.1002/pmic.202400028.

Multi-omics exploration of biomolecular corona in nanomedicine therapeutics and diagnostics.

Saei A, Mahmoudi M Nanomedicine (Lond). 2024; 19(14):1223-1226.

PMID: 38593028 PMC: 11285268. DOI: 10.2217/nnm-2024-0104.

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