Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment
Abstract
Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein 'corona'. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein-nanomaterial interactions. We conclude by discussing gaps in the understanding of protein-nanomaterial interactions along with strategies to fill them (167 references).
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The functionalized NPs possess unique advantages over antibody-based platforms: comparable size and diffusion kinetics to proteins, high surface area per volume and high number of flexible binding sites, and inexpensive, simple, fast, scalable synthesis with minimal batch-to-batch variability.
“These results highlight the unique advantages that these functionalized NPs possess for protein enrichment over antibody-based platforms: (a) comparable size and diffusion kinetics to proteins, promoting effective capture of low-abundance proteins within complex mixtures20,47,48; (b) high surface area per volume and high number of flexible binding sites, contributing to high ligand density and”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [47]
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- Authors
- Walkey, C. D., & Chan, W. C. W.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Chan, Warren C. W.
- Venue
- Chem. Soc. Rev.
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2012
- Volume
- 41
- Issue
- 7
- Pages
- 2780-2799
- ISSN
- 0306-0012 (ISSN-L)
- 1460-4744
- OpenAlex
- W2050886209
- Semantic Scholar
- 6bbd11034b2cd65f93db0d76f9f40e092a5ccc5e
- Cited by
- 1,758
- References
- 165
- Citations by year
- 2026: 146 · 2025: 83 · 2024: 94 · 2023: 120 · 2022: 114 · 2021: 129 · 2020: 162 · 2019: 144 · 2018: 135 · 2017: 121 · 2016: 138 · 2015: 138 · 2014: 124 · 2013: 75 · 2012: 31
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemical Society Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Physical Sciences › Engineering › Biomedical Engineering › Nanotechnology research and applications
- Keywords
- protein corona, nanomaterial-protein interactions, plasma proteins, nanomaterial toxicity, nanomaterial design, physiological environment, interfacial composition
- MeSH terms
- Adsorption, Animals, Humans, Kinetics, Models, Biological, Particle Size, Proteins, Nanoparticles
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