title: Temperature-Triggered Protein Adsorption on Polymer-Coated Nanoparticles in Serum.
abstract: The protein corona, which forms on the nanoparticle's surface in most biological media, determines the nanoparticle's physicochemical characteristics. The formation of the protein corona has a significant impact on the biodistribution and clearance of nanoparticles in vivo. Therefore, the ability to influence the formation of the protein corona is essential to most biomedical applications, including drug delivery and imaging. In this study, we investigate the protein adsorption on nanoparticles with a hydrodynamic radius of 30 nm and a coating of thermoresponsive poly(2-isopropyl-2-oxazoline) in serum. Using multiangle dynamic light scattering (DLS) we demonstrate that heating of the nanoparticles above their phase separation temperature induces the formation of agglomerates, with a hydrodynamic radius of 1 μm. In serum, noticeably stronger agglomeration occurs at lower temperatures compared to serum-free conditions. Cryogenic transmission electron microscopy (cryo-TEM) revealed a high packing density of agglomerates when serum was not present. In contrast, in the presence of serum, agglomerated nanoparticles were loosely packed, indicating that proteins are intercalated between them. Moreover, an increase in protein content is observed upon heating, confirming that protein adsorption is induced by the alteration of the surface during phase separation. After cooling and switching the surface back, most of the agglomerates were dissolved and the main fraction returned to the original size of approximately 30 nm as shown by asymmetrical flow-field flow fractionation (AF-FFF) and DLS. Furthermore, the amounts of adsorbed proteins are similar before and after heating the nanoparticles to above their phase-separation temperature. Overall, our results demonstrate that the thermoresponsivity of the polymer coating enables turning the corona formation on nanoparticles on and off in situ. As the local heating of body areas can be easily done in vivo, the thermoresponsive coating could potentially be used to induce the agglomeration of nanoparticles and proteins and the accumulation of nanoparticles in a targeted body region.
authors.affiliation: †Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.|‡BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Koshkina
authors.affiliation: †Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.|‡BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lang
authors.affiliation: †Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Thiermann
authors.affiliation: §Department of Nanobiomedicine/ENT, University Medical Center of Mainz, Langenbeckstraße 1, 55101 Mainz, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Docter
authors.affiliation: §Department of Nanobiomedicine/ENT, University Medical Center of Mainz, Langenbeckstraße 1, 55101 Mainz, Germany.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stauber
authors.affiliation: ∥Department of Colloid Chemistry, Max Planck Institute of Colloids and Interfaces, Research Campus Golm, 14424 Potsdam, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Secker
authors.affiliation: ⊥University of Potsdam, Institute of Chemistry, Karl-Liebknecht-Straße 24-25, 14476 Potsdam, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schlaad
authors.affiliation: ‡BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Weidner
authors.affiliation: †Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mohr
authors.affiliation: †Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129 Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Maskos
authors.affiliation: ‡BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin, Germany.|#Institute of Chemistry and Biochemistry - Organic Chemistry, Free University Berlin, Takustraße 3, 14195 Berlin, Germany.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Bertin
mesh_terms: D000327:Adsorption; D057446:Hydrodynamics; D053758:Nanoparticles / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry*; D010316:Particle Size; D000066970:Protein Corona / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
chemical_list: D010080:Oxazoles; D000066970:Protein Corona; C000605739:poly(2-isopropyl-2-oxazoline)