Polymeric Nanoparticles with Neglectable Protein Corona
Small, vol. 16, pp. e1907574
Abstract
The current understanding of nanoparticle-protein interactions indicates that they rapidly adsorb proteins upon introduction into a living organism. The formed protein corona determines thereafter identity and fate of nanoparticles in the body. The present study evaluates the protein affinity of three core-crosslinked polymeric nanoparticles with long circulation times, differing in the hydrophilic polymer material forming the particle surface, namely poly(N-2-hydroxypropylmethacrylamide) (pHPMA), polysarcosine (pSar), and poly(ethylene glycol) (PEG). This includes the nanotherapeutic CPC634, which is currently in clinical phase II evaluation. To investigate possible protein corona formation, the nanoparticles are incubated in human blood plasma and separated by asymmetrical flow field-flow fractionation (AF4). Notably, light scattering shows no detectable differences in particle size or polydispersity upon incubation with plasma for all nanoparticles, while in gel electrophoresis, minor amounts of proteins can be detected in the particle fraction. Label-free quantitative proteomics is additionally applied to analyze and quantify the composition of the proteins. It proves that some proteins are enriched, but their concentration is significantly less than one protein per particle. Thus, most of the nanoparticles are not associated with any proteins. Therefore, this work underlines that polymeric nanoparticles can be synthesized, for which a protein corona formation does not take place.
Authors 16
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Johannes Gutenberg University Mainz
Affiliation as printed
Institute of Organic Chemistry Johannes Gutenberg University Mainz Duesbergweg 10‐14 Mainz D‐55128 Germany
Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, D-55128 Germany
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Johannes Gutenberg University Mainz
Affiliation as printed
Institute of Physical Chemistry Johannes Gutenberg University Mainz Duesbergweg 10‐14 Mainz D‐55128 Germany
Institute of Physical Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, D-55128 Germany
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Cristal Therapeutics (Netherlands)
Affiliation as printed
Cristal Therapeutics Oxfordlaan 55 Maastricht 6229 EV The Netherlands
Cristal Therapeutics, Oxfordlaan 55, Maastricht, 6229 EV The Netherlands
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Johannes Gutenberg University Mainz
Affiliation as printed
Institute of Organic Chemistry Johannes Gutenberg University Mainz Duesbergweg 10‐14 Mainz D‐55128 Germany
Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, D-55128 Germany
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University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Immunology University Medical Center of Mainz Langenbeckstr. 1 Mainz 55131 Germany
Institute for Immunology, University Medical Center of Mainz, Langenbeckstr. 1, Mainz, 55131 Germany
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Natascha Drude Aachen Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Forckenbecktrasse 55 Aachen 52074 Germany
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Forckenbecktrasse 55, Aachen, 52074 Germany
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Diana Möckel Aachen Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Forckenbecktrasse 55 Aachen 52074 Germany
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Forckenbecktrasse 55, Aachen, 52074 Germany
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Cristal Therapeutics (Netherlands)
Affiliation as printed
Cristal Therapeutics Oxfordlaan 55 Maastricht 6229 EV The Netherlands
Cristal Therapeutics, Oxfordlaan 55, Maastricht, 6229 EV The Netherlands
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Twan Lammers Aachen Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Forckenbecktrasse 55 Aachen 52074 Germany
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Forckenbecktrasse 55, Aachen, 52074 Germany
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University Medical Center of the Johannes Gutenberg University Mainz · Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Affiliation as printed
TRON ‐ Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH Freiligrathstr. 12 Mainz 55131 Germany
TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH, Freiligrathstr. 12, Mainz, 55131 Germany
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Fraunhofer Institute for Microengineering and Microsystems
Affiliation as printed
Fraunhofer Institute for Microengineering and Microsystems IMM Carl‐Zeiss‐Str. 18‐20 Mainz 55129 Germany
Fraunhofer Institute for Microengineering and Microsystems IMM, Carl-Zeiss-Str. 18-20, Mainz, 55129 Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 Germany
Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz, 55128 Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 Germany
Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz, 55128 Germany
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Stefan Tenzer corresponding
University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Immunology University Medical Center of Mainz Langenbeckstr. 1 Mainz 55131 Germany
Institute for Immunology, University Medical Center of Mainz, Langenbeckstr. 1, Mainz, 55131 Germany
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Matthias Barz corresponding
Johannes Gutenberg University Mainz
Affiliation as printed
Institute of Organic Chemistry Johannes Gutenberg University Mainz Duesbergweg 10‐14 Mainz D‐55128 Germany
Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, D-55128 Germany
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Rudolf Zentel corresponding
Johannes Gutenberg University Mainz
Affiliation as printed
Institute of Organic Chemistry Johannes Gutenberg University Mainz Duesbergweg 10‐14 Mainz D‐55128 Germany
Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz, D-55128 Germany
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