title: Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization.
abstract: In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.
authors.affiliation: Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Bachstraße 18, D-07740 Jena, Germany ; Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Forschungszentrum Lobeda, Erlanger Allee 111, D-07747 Jena, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Landgraf
authors.affiliation: Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Bachstraße 18, D-07740 Jena, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Müller
authors.affiliation: Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Bachstraße 18, D-07740 Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ernst
authors.affiliation: Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Bachstraße 18, D-07740 Jena, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Institut für Physikalische Chemie, Johannes Gutenberg Universität Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rosman
authors.affiliation: Johannes Gutenberg-Universität, Institut für Anorganische Chemie und Analytische Chemie, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Schick
authors.affiliation: Johannes Gutenberg-Universität, Institut für Anorganische Chemie und Analytische Chemie, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Oskar
authors.initials: O
authors.lastname: Köhler
authors.affiliation: Institut für Anatomie II, Universitätsklinikum Jena, Teichgraben 7, D-07743 Jena, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Oehring
authors.affiliation: Institut für Physikalische Chemie, Johannes Gutenberg Universität Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Breus
authors.affiliation: Institut für Physikalische Chemie, Johannes Gutenberg Universität Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Basché
authors.affiliation: Institut für Physikalische Chemie, Johannes Gutenberg Universität Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Sönnichsen
authors.affiliation: Johannes Gutenberg-Universität, Institut für Anorganische Chemie und Analytische Chemie, Duesbergweg 10-14, D-55128 Mainz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tremel
authors.affiliation: Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Bachstraße 18, D-07740 Jena, Germany ; Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Forschungszentrum Lobeda, Erlanger Allee 111, D-07747 Jena, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
keywords: Janus particles; cell viability; gold nanoparticles; internalization; quantum dots
references.citation: Small. 2007 Nov;3(11):1941-9
references.pmid: 17963284
references.citation: Angew Chem Int Ed Engl. 2009;48(50):9477-80
references.pmid: 19899173
references.citation: Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7896-900
references.pmid: 1881923
references.citation: ACS Nano. 2009 Dec 22;3(12):4110-6
references.pmid: 19919048
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11613-8
references.pmid: 18697944
references.citation: Biomaterials. 2011 Sep;32(26):6291-301
references.pmid: 21684593
references.citation: Chem Rev. 2011 Jun 8;111(6):3828-57
references.pmid: 21648956
references.citation: Biomacromolecules. 2010 Oct 11;11(10):2675-82
references.pmid: 20863132
references.citation: Nat Biotechnol. 2004 Jan;22(1):93-7
references.pmid: 14661026
references.citation: Angew Chem Int Ed Engl. 2008;47(1):173-6
references.pmid: 17992677
references.citation: ACS Nano. 2013 Oct 22;7(10):9040-8
references.pmid: 24047405
references.citation: Beilstein J Nanotechnol. 2014 Sep 24;5:1625-36
references.pmid: 25383275
references.citation: Science. 2003 May 30;300(5624):1434-6
references.pmid: 12775841
references.citation: J Am Chem Soc. 2006 Jul 5;128(26):8378-9
references.pmid: 16802785
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15752-6
references.pmid: 16239346
references.citation: Chem Soc Rev. 2012 Apr 7;41(7):2740-79
references.pmid: 22109657
references.citation: J Am Chem Soc. 2014 Feb 12;136(6):2473-83
references.pmid: 24460244
references.citation: Toxicol Appl Pharmacol. 2010 Jul;246(1-2):83-90
references.pmid: 20417650
references.citation: Biomaterials. 2013 Jul;34(21):5163-71
references.pmid: 23591395
references.citation: J Mol Med (Berl). 2005 May;83(5):377-85
references.pmid: 15688234
references.citation: Nat Nanotechnol. 2008 Mar;3(3):145-50
references.pmid: 18654486
references.citation: Nanomedicine. 2009 Jun;5(2):106-17
references.pmid: 19071065
references.citation: Angew Chem Int Ed Engl. 2010 May 25;49(23 ):3976-80
references.pmid: 20408148
references.citation: Pharm Res. 2014 Dec;31(12):3274-88
references.pmid: 24890197
references.citation: J Appl Toxicol. 2010 Apr;30(3):212-7
references.pmid: 19902477
references.citation: Nat Mater. 2004 Dec;3(12):891-5
references.pmid: 15568032
references.citation: Biochem J. 1993 Dec 1;296 ( Pt 2):297-301
references.pmid: 8257416
references.citation: Bioconjug Chem. 2005 Sep-Oct;16(5):1181-8
references.pmid: 16173796
references.citation: Small. 2012 Dec 7;8(23):3683-90
references.pmid: 22888068
references.citation: J Phys Chem B. 2006 Oct 5;110(39):19220-5
references.pmid: 17004772
references.citation: Nat Biotechnol. 2004 Aug;22(8):969-76
references.pmid: 15258594
references.citation: ACS Nano. 2009 Sep 22;3(9):2573-80
references.pmid: 19719085
references.citation: Biochem J. 2004 Jan 1;377(Pt 1):159-69
references.pmid: 14505488
references.citation: J Cell Sci. 2001 Oct;114(Pt 20):3737-47
references.pmid: 11707525
references.citation: Acta Pol Pharm. 2000 Mar-Apr;57(2):135-55
references.pmid: 10934794
references.citation: Nat Mater. 2008 Aug;7(8):659-64
references.pmid: 18568030
references.citation: Biomaterials. 2010 Oct;31(30):7606-19
references.pmid: 20656344
references.citation: J Pharm Pharmacol. 2014 Apr;66(4):564-73
references.pmid: 24635558
references.citation: Cancer. 2010 Jul 1;116(13):3285-93
references.pmid: 20564640
references.citation: Talanta. 2012 Apr 15;92:72-7
references.pmid: 22385810
references.citation: Chem Phys Lett. 2008 Sep 20;463(1-3):145-149
references.pmid: 24068836
references.citation: J Am Chem Soc. 2009 Apr 1;131(12):4216-7
references.pmid: 19275156
references.citation: ACS Appl Mater Interfaces. 2010 Oct;2(10 ):2949-55
references.pmid: 20929249
references.citation: Macromol Biosci. 2008 Dec 8;8(12):1135-43
references.pmid: 18698581
references.citation: Langmuir. 2013 Jul 23;29(29):9138-48
references.pmid: 23815604
references.citation: Anticancer Res. 2007 Jul-Aug;27(4A):2019-22
references.pmid: 17649815
references.citation: Chem Commun (Camb). 2011 Apr 21;47(15):4382-4
references.pmid: 21390403
references.citation: Nanoscale. 2013 May 7;5(9):3723-32
references.pmid: 23334060
references.citation: Nano Lett. 2005 May;5(5):829-34
references.pmid: 15884879
references.citation: Pharmazie. 2010 Mar;65(3):199-201
references.pmid: 20383940
references.citation: Bioconjug Chem. 2010 Jun 16;21(6):1070-8
references.pmid: 20476781
references.citation: Acc Chem Res. 2009 Aug 18;42(8):1097-107
references.pmid: 19476332
references.citation: J Cell Biol. 1994 Dec;127(5):1199-215
references.pmid: 7962085
references.citation: J Phys Chem B. 2006 Apr 13;110(14):7238-48
references.pmid: 16599493
references.citation: J Cell Biol. 1993 Dec;123(5):1107-17
references.pmid: 8245121
references.citation: J Am Chem Soc. 2007 Jun 20;129(24):7661-5
references.pmid: 17530850
references.citation: J Control Release. 2006 Sep 12;114(3):343-7
references.pmid: 16876898
references.citation: Int J Nanomedicine. 2011;6:3219-31
references.pmid: 22238510
references.citation: Pharmacol Rev. 2006 Mar;58(1):32-45
references.pmid: 16507881
references.citation: ACS Nano. 2010 Jun 22;4(6):3073-86
references.pmid: 20507158
references.citation: Small. 2009 Mar;5(6):701-8
references.pmid: 19226599
references.citation: J Cell Biol. 1998 May 18;141(4):905-15
references.pmid: 9585410
references.citation: ACS Nano. 2009 Jan 27;3(1):213-22
references.pmid: 19206269
references.citation: Biotechnol Bioeng. 2011 Dec;108(12):2988-98
references.pmid: 21766288