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Impact of protein pre-coating on the protein corona composition and nanoparticle cellular uptake
Abstract
Nanoparticles (NPs) are functionalized with targeting ligands to enable selectively delivering drugs to desired locations in the body. When these functionalized NPs enter the blood stream, plasma proteins bind to their surfaces, forming a protein corona that affects NP uptake and targeting efficiency. To address this problem, new strategies for directing the formation of a protein corona that has targeting capabilities are emerging. Here, we have investigated the feasibility of directing corona composition to promote targeted NP uptake by specific types of cells. We used the well-characterized process of opsonin-induced phagocytosis by macrophages as a simplified model of corona-mediated NP uptake by a desired cell type. We demonstrate that pre-coating silica NPs with gamma-globulins (γ-globulins) produced a protein corona that was enriched with opsonins, such as immunoglobulins. Although immunoglobulins are ligands that bind to receptors on macrophages and elicit phagocytois, the opsonin-rich protein corona did not increase NP uptake by macrophage RAW 264.7 cells. Immunolabeling experiments indicated that the binding of opsonins to their target cell surface receptors was impeded by other proteins in the corona. Thus, corona-mediated NP targeting strategies must optimize both the recruitment of the desired plasma proteins as well as their accessibility and orientation in the corona layer.
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These strategies are still limited at conferring targeting specificity because an additional targeting ligand increases the propensity for protein corona formation to mask targeting ability and inhibit the biological effects of nanoparticles.
“these strategies are still limited at conferring targeting specificity since an additional targeting ligand increases the propensity for protein corona formation to mask the targeting ability and inhibit the biological effects of nanoparticles18–24.”
From Cloaking nanoparticles with protein corona shield for targeted drug delivery. (2018) · cites this paper as [19]
Covalent attachment of counterparts on particles significantly changes their conformations and particle surface properties, inducing potential detrimental interactions with external biomolecules rather than stabilizing them.
“covalent attachment of their counterparts on particles significantly changes their conformations and particle surface properties (e.g., hydrophobicity and charge density), inducing potential detrimental interactions with external biomolecules, rather than stabilizing them13,19,37.”
From Cloaking nanoparticles with protein corona shield for targeted drug delivery. (2018) · cites this paper as [19]
The orientation of functional plasma proteins in the corona layer is random and their accessibility to receptor-binding pocket is impaired.
“One possible reason is that the orientation of functional plasma proteins in the corona layer is random and their accessibility to receptor-binding pocket is impaired22,23.”
From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [22]
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Metadata
- Authors
- Mirshafiee, V., Kim, R., Park, S., Mahmoudi, M., & Kraft, M. L.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Stanford Medicine (US)
- Corresponding author
- Mahmoudi, Morteza
- Kraft, Mary L.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 75
- Pages
- 295-304
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2177773825
- Cited by
- 316
- References
- 0
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 20 · 2023: 27 · 2022: 40 · 2021: 32 · 2020: 45 · 2019: 28 · 2018: 33 · 2017: 31 · 2016: 20
- FWCI
- 10.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- 3M Corporate Fellowship
- Drickamer Graduate Research Fellowship
- University of Illinois
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Keywords
- protein corona, opsonization, opsonins, immunoglobulins, macrophage phagocytosis, silica nanoparticles, plasma protein binding, RAW 264.7 macrophages
- MeSH terms
- Protein Corona, RAW 264.7 Cells, Animals, Chromatography, Liquid, Electrophoresis, Polyacrylamide Gel, Endocytosis, Flow Cytometry, gamma-Globulins, Humans, Particle Size, Receptors, Fc, Serum Albumin, Microscopy, Confocal, Mice, Tandem Mass Spectrometry, Nanoparticles, Static Electricity, Hydrodynamics
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