title: Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers.
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.
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.|Johannes Gutenberg University Mainz, University Medical Center, Department of Dermatology, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schöttler
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Greta
authors.initials: G
authors.lastname: Becker
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Winzen
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Steinbach
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Mohr
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.|Johannes Gutenberg University Mainz, University Medical Center, Department of Dermatology, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Frederik R
authors.initials: FR
authors.lastname: Wurm
mesh_terms: D000327:Adsorption; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism*; D051152:Clusterin; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D051152:Clusterin; D004337:Drug Carriers; D011091:Polyesters; D011092:Polyethylene Glycols