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Cited by 599Nanoparticle-Based Drug DeliveryComplement system in diseasesCharacterization and Applications of Magnetic Nanoparticles

Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo

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Chen, Fangfang, Wang, Guankui, Griffin, James I., Brenneman, Barbara, Banda, Nirmal K., Holers, V. Michael, Backos, Donald S., Wu, LinPing +2 more·2017·Nature Nanotechnology
DOI 10.1038/nnano.2016.269PMC PMC5617637
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Abstract

When nanoparticles are intravenously injected into the body, complement proteins deposit on the surface of nanoparticles in a process called opsonization. These proteins prime the particle for removal by immune cells and may contribute toward infusion-related adverse effects such as allergic responses. The ways complement proteins assemble on nanoparticles have remained unclear. Here, we show that dextran-coated superparamagnetic iron oxide core-shell nanoworms incubated in human serum and plasma are rapidly opsonized with the third complement component (C3) via the alternative pathway. Serum and plasma proteins bound to the nanoworms are mostly intercalated into the nanoworm shell. We show that C3 covalently binds to these absorbed proteins rather than the dextran shell and the protein-bound C3 undergoes dynamic exchange in vitro. Surface-bound proteins accelerate the assembly of the complement components of the alternative pathway on the nanoworm surface. When nanoworms pre-coated with human plasma were injected into mice, C3 and other adsorbed proteins undergo rapid loss. Our results provide important insight into dynamics of protein adsorption and complement opsonization of nanomedicines.

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  • Protein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution.

    “Protein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution.”

    From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [10]

    The introductory passage labeled Abstract (page unavailable) says the protein coat may affect nanoparticle targeting, pharmacokinetics and biodistribution; the paper also reports complement-mediated immune uptake. It does not establish that the corona severely reduces targeting yields, causes unfavorable biodistribution, or is a major obstacle to clinical translation. (LLM, conf=0.86)

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Cited by

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Authors
Chen, F., Wang, G., Griffin, J. I., Brenneman, B., Banda, N. K., Holers, V. M., Backos, D. S., Wu, L., Moghimi, S. M., & Simberg, D.
Affiliations
  • Jilin University (CN)
  • University of Colorado Anschutz (US)
  • University of Copenhagen (DK)
Corresponding author
Simberg, Dmitri
ORCID
Venue
Nature Nanotechnology
Publisher
Springer Science and Business Media LLC
Published
2016-12-19
Volume
12
Issue
4
Pages
387-393
ISSN
  • 1748-3387 (ISSN-L)
  • 1748-3395
DOI
10.1038/nnano.2016.269
PMC
PMC5617637
OpenAlex
W2562957244
Cited by
599
References
2
Citations by year
2026: 69 · 2025: 68 · 2024: 48 · 2023: 53 · 2022: 70 · 2021: 68 · 2020: 84 · 2019: 61 · 2018: 49 · 2017: 28 · 2016: 1
FWCI
16.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Nanotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR001082)
  • University of Colorado Denver
  • National Institute of Biomedical Imaging and Bioengineering (R01EB022040)
  • National Center for Advancing Translational Sciences
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
  • Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
Keywords
complement proteins, protein corona, alternative complement pathway, complement C3, dextran coating, covalent binding, nanomedicine
MeSH terms
Complement Pathway, Alternative, Complement C3, Dextrans, Humans, Coated Materials, Biocompatible, Magnetite Nanoparticles

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