title: Fluoromica nanoparticle cytotoxicity in macrophages decreases with size and extent of uptake.
abstract: Polyurethanes are widely used in biomedical devices such as heart valves, pacemaker leads, catheters, vascular devices, and surgical dressings because of their excellent mechanical properties and good biocompatibility. Layered silicate nanoparticles can significantly increase tensile strength and breaking strain of polyurethanes potentially increasing the life span of biomedical devices that suffer from wear in vivo. However, very little is known about how these nanoparticles interact with proteins and cells and how they might exert unwanted effects. A series of fluoromica nanoparticles ranging in platelet size from 90 to over 600 nm in diameter were generated from the same base material ME100 by high energy milling and differential centrifugation. The cytotoxicity of the resulting particles was dependent on platelet size but in a manner that is opposite to many other types of nanomaterials. For the fluoromicas, the smaller the platelet size, the less toxicity was observed. The small fluoromica nanoparticles (<200 nm) were internalized by macrophages via scavenger receptors, which was dependent on the protein corona formed in serum. This internalization was associated with apoptosis in RAW cells but not in dTHP-1 cells. The larger particles were not internalized efficiently but mostly decorated the surface of the cells, causing membrane disruption, even in the presence of 80% serum. This work suggests the smaller fluoromica platelets may be safer for use in humans but their propensity to recognize macrophage scavenger receptors also suggests that they will target the reticulo-endoplasmic system in vivo.
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Nicolin
authors.initials: N
authors.lastname: Tee
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Gysell M
authors.initials: GM
authors.lastname: Mortimer
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Martin
authors.affiliation: School of Biomedical Science, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Rodney F
authors.initials: RF
authors.lastname: Minchin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D000067996:RAW 264.7 Cells
chemical_list: D005456:Fluorescent Dyes
keywords: accumulation; high energy milling; layered silicates; phagocytosis
references.citation: Toxicology. 2005 Sep 15;213(1-2):66-73
references.pmid: 15970370
references.citation: J Mater Sci Mater Med. 2010 Aug;21(8):2307-16
references.pmid: 20033261
references.citation: Biomaterials. 2011 Dec;32(36):9810-7
references.pmid: 21944826
references.citation: Biomaterials. 2007 Jul;28(19):2946-58
references.pmid: 17379299
references.citation: Small. 2009 Apr;5(7):846-53
references.pmid: 19288475
references.citation: Small. 2011 May 23;7(10):1322-37
references.pmid: 21520409
references.citation: Nat Nanotechnol. 2008 Mar;3(3):145-50
references.pmid: 18654486
references.citation: Inhal Toxicol. 2007 Aug;19(10):849-56
references.pmid: 17687716
references.citation: Environ Health Perspect. 2007 May;115(5):728-33
references.pmid: 17520060
references.citation: Nanotoxicology. 2010 Sep;4(3):307-18
references.pmid: 20795912
references.citation: J Aerosol Med Pulm Drug Deliv. 2010 Aug;23(4):207-17
references.pmid: 20109124
references.citation: Nat Nanotechnol. 2012 Dec;7(12):779-86
references.pmid: 23212421
references.citation: Biomaterials. 2005 Dec;26(35):7457-70
references.pmid: 16024077
references.citation: Crit Rev Toxicol. 2009;39(7):613-26
references.pmid: 19650720
references.citation: J Lipid Res. 1999 Sep;40(9):1647-54
references.pmid: 10484611
references.citation: J Pharm Sci. 2009 Dec;98(12):4831-43
references.pmid: 19544368
references.citation: Small. 2009 Mar;5(3):389-99
references.pmid: 19148889
references.citation: Toxicol In Vitro. 2012 Sep;26(6):799-806
references.pmid: 22664788
references.citation: Biomaterials. 2012 Oct;33(28):6858-67
references.pmid: 22770526
references.citation: Toxicol Appl Pharmacol. 2002 Oct 15;184(2):98-106
references.pmid: 12408954
references.citation: Int J Pharm. 2008 Jul 9;359(1-2):198-204
references.pmid: 18502063
references.citation: Toxicol In Vitro. 2005 Oct;19(7):975-83
references.pmid: 16125895
references.citation: Toxicol Appl Pharmacol. 2001 Jul 1;174(1):10-6
references.pmid: 11437644
references.citation: Semin Immunol. 2008 Apr;20(2):86-100
references.pmid: 18162407
references.citation: ACS Nano. 2014 Apr 22;8(4):3357-66
references.pmid: 24617595
references.citation: J Cell Biol. 2005 Oct 10;171(1):61-73
references.pmid: 16203857
references.citation: Toxicol Appl Pharmacol. 1996 Nov;141(1):84-92
references.pmid: 8917679
references.citation: Acc Chem Res. 2004 May;37(5):326-33
references.pmid: 15147173