title: Protein source and choice of anticoagulant decisively affect nanoparticle protein corona and cellular uptake.
abstract: Protein adsorption on nanoparticles has been a focus of the field of nanocarrier research in the past few years and more and more papers are dealing with increasingly detailed lists of proteins adsorbed to a plethora of nanocarriers. While there is an urgent need to understand the influence of this protein corona on nanocarriers' interactions with cells the strong impact of the protein source on corona formation and the consequence for interaction with different cell types are factors that are regularly neglected, but should be taken into account for a meaningful analysis. In this study, the importance of the choice of protein source used for in vitro protein corona analysis is concisely investigated. Major and decisive differences in cellular uptake of a polystyrene nanoparticle incubated in fetal bovine serum, human serum, human citrate and heparin plasma are reported. Furthermore, the protein compositions are determined for coronas formed in the respective incubation media. A strong influence of heparin, which is used as an anticoagulant for plasma generation, on cell interaction is demonstrated. While heparin enhances the uptake into macrophages, it prevents internalization into HeLa cells. Taken together we can give the recommendation that human plasma anticoagulated with citrate seems to give the most relevant results for in vitro studies of nanoparticle uptake.
authors.affiliation: Max Planck Institute of Polymer Research, Ackermannweg 10, 55128 Mainz, Germany. volker.mailaender@unimedizin-mainz.de and Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schöttler
authors.affiliation: Max Planck Institute of Polymer Research, Ackermannweg 10, 55128 Mainz, Germany. volker.mailaender@unimedizin-mainz.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Klein
authors.affiliation: Max Planck Institute of Polymer Research, Ackermannweg 10, 55128 Mainz, Germany. volker.mailaender@unimedizin-mainz.de.
authors.forename: K
authors.initials: K
authors.lastname: Landfester
authors.affiliation: Max Planck Institute of Polymer Research, Ackermannweg 10, 55128 Mainz, Germany. volker.mailaender@unimedizin-mainz.de and Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Mailänder
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry*; D001774:Blood Chemical Analysis / Q000379:methods*; D002417:Cattle; D002853:Chromatography, Liquid; D019343:Citric Acid / Q000737:chemistry; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D013058:Mass Spectrometry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010949:Plasma / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D000066970:Protein Corona / Q000737:chemistry*; D044967:Serum / Q000737:chemistry*
chemical_list: D000925:Anticoagulants; D011137:Polystyrenes; D000066970:Protein Corona; D019343:Citric Acid; D006493:Heparin