Tuning the Surface of Nanoparticles: Impact of Poly(2-ethyl-2-oxazoline) on Protein Adsorption in Serum and Cellular Uptake.
Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asymmetrical flow field-flow fractionation, gel electrophoresis, and liquid chromatography-mass spectrometry, it is demonstrated that protein adsorption on PEtOxylated nanoparticles is extremely low, similar as on PEGylated nanoparticles. Moreover, quantitative microscopy reveals that PEtOxylation significantly reduces the non-specific cellular uptake, particularly by macrophage-like cells. Collectively, studies demonstrate that PEtOx is a very effective alternative to PEG for stealth modification of the surface of nanoparticles.
Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129, Mainz, Germany. Olga.Koshkina@radboudumc.nl.|BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205, Berlin, Germany. Olga.Koshkina@radboudumc.nl.
Olga
O
Koshkina
Molecular and Cellular Oncology, University Medical Center of Johannes Gutenberg-University Mainz.
Dana
D
Westmeier
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.
Thomas
T
Lang
Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129, Mainz, Germany.
Christoph
C
Bantz
Molecular and Cellular Oncology, University Medical Center of Johannes Gutenberg-University Mainz.
Angelina
A
Hahlbrock
BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205, Berlin, Germany.
Christian
C
Würth
BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205, Berlin, Germany.
Ute
U
Resch-Genger
BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205, Berlin, Germany.
Ulrike
U
Braun
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.
Raphael
R
Thiermann
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195, Berlin, Germany.
Christoph
C
Weise
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195, Berlin, Germany.
Murat
M
Eravci
Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129, Mainz, Germany.
Benjamin
B
Mohr
Institute of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476, Potsdam, Germany.
Helmut
H
Schlaad
Molecular and Cellular Oncology, University Medical Center of Johannes Gutenberg-University Mainz.
Roland H
RH
Stauber
Molecular and Cellular Oncology, University Medical Center of Johannes Gutenberg-University Mainz. Docter@uni-mainz.de.
Dominic
D
Docter
BAM Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205, Berlin, Germany.|Institute of Chemistry and Biochemistry - Organic Chemistry, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
Annabelle
A
Bertin
Fraunhofer ICT-IMM, Carl-Zeiss-Str. 18-20, 55129, Mainz, Germany. Michael.Maskos@imm.fraunhofer.de.
Michael
M
Maskos
D000327:Adsorption; D002460:Cell Line; D005591:Chemical Fractionation; D000067493:Dynamic Light Scattering; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012235:Rhodamines / Q000378:metabolism; D044967:Serum / Q000378:metabolism*; D013499:Surface Properties; D013997:Time Factors
D011073:Polyamines; D011506:Proteins; D012235:Rhodamines; C511916:poly(2-ethyl-2-oxazoline); C029773:rhodamine B
cellular uptake; nanoparticles; poly(2-ethyl-2-oxazoline); poly(ethylene glycol); protein adsorption