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Tuning the Surface of Nanoparticles: Impact of Poly(2‐ethyl‐2‐oxazoline) on Protein Adsorption in Serum and Cellular Uptake
Authors:Olga Koshkina  Dana Westmeier  Thomas Lang  Christoph Bantz  Angelina Hahlbrock  Christian Würth  Ute Resch‐Genger  Ulrike Braun  Raphael Thiermann  Christoph Weise  Murat Eravci  Benjamin Mohr  Helmut Schlaad  Roland H Stauber  Dominic Docter  Annabelle Bertin  Michael Maskos
Institution:1. Fraunhofer ICT‐IMM, Mainz, Germany;2. BAM Federal Institute for Materials Research and Testing, Berlin, GermanyPresent address: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 26/28, 6525 GA, Nijmegen, The Netherlands;3. Molecular and Cellular OncologyUniversity Medical Center of Johannes Gutenberg‐University Mainz;4. BAM Federal Institute for Materials Research and Testing, Berlin, Germany;5. Institute of Chemistry and Biochemistry, Freie Universit?t Berlin, Berlin, Germany;6. Institute of Chemistry, University of Potsdam, Potsdam, Germany;7. Institute of Chemistry and Biochemistry – Organic Chemistry, Freie Universit?t Berlin, Berlin, Germany
Abstract: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.
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Keywords:cellular uptake  nanoparticles  poly(2‐ethyl‐2‐oxazoline)  poly(ethylene glycol)  protein adsorption
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