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Cited by 1,272Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsDendrimers and Hyperbranched Polymers

Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers

Schöttler, Susanne, Becker, Greta, Winzen, Svenja, Steinbach, Tobias, Mohr, Kristin, Landfester, Katharina, Mailänder, Volker, Wurm, Frederik R.·2016·Nature Nanotechnology
DOI 10.1038/nnano.2015.330
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Abstract

The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake.

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Crossref · 10.1038/nnano.2015.330

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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 [21]

  • Apolipoproteins have been reported as dysopsonins.

    “Apolipoproteins have been reported as dysopsonins44,45.”

    From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [44]

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Authors
Schöttler, S., Becker, G., Winzen, S., Steinbach, T., Mohr, K., Landfester, K., Mailänder, V., & Wurm, F. R.
Affiliations
  • Johannes Gutenberg University Mainz (DE)
  • Max Planck Institute for Polymer Research (DE)
Corresponding author
  • Mailänder, Volker
  • Wurm, Frederik R.
ORCID
Venue
Nature Nanotechnology
Publisher
Springer Science and Business Media LLC
Published
2016-02-15
Volume
11
Issue
4
Pages
372-377
ISSN
  • 1748-3387 (ISSN-L)
  • 1748-3395
DOI
10.1038/nnano.2015.330
OpenAlex
W2284550715
Cited by
1,272
References
2
Citations by year
2026: 91 · 2025: 99 · 2024: 110 · 2023: 99 · 2022: 142 · 2021: 129 · 2020: 151 · 2019: 135 · 2018: 134 · 2017: 125 · 2016: 55 · 2015: 1
FWCI
61.12
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Nanotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
protein adsorption, stealth effect, polyethylene glycol, protein corona, clusterin, plasma proteins, drug carriers, nanoparticle surface modification
MeSH terms
Adsorption, Blood Proteins, Drug Carriers, Humans, Polyesters, Polyethylene Glycols, Clusterin, Nanoparticles

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