title: Nanoparticle geometry and surface orientation influence mode of cellular uptake.
abstract: In order to engineer safer nanomaterials, there is a need to understand, systematically evaluate, and develop constructs with appropriate cellular uptake and intracellular fates. The overall goal of this project is to determine the uptake patterns of silica nanoparticle geometries in model cells, in order to aid in the identification of the role of geometry on cellular uptake and transport. In our experiments we observed a significant difference in the viability of two phenotypes of primary macrophages; immortalized macrophages exhibited similar patterns. However, both primary and immortalized epithelial cells did not exhibit toxicity profiles. Interestingly uptake of these geometries in all cell lines exhibited very different time-dependent patterns. A screening of a series of chemical inhibitors of endocytosis was performed to isolate the uptake mechanisms of the different particles. The results show that all geometries exhibit very different uptake profiles and that this may be due to the orientation of the nanoparticles when they interact with the cell surface. Additionally, evidence suggests that these uptake patterns initialize different downstream cellular pathways, dependent on cell type and phenotype.
authors: Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, 36 S. Wasatch Drive, Salt Lake City, Utah 84112, United States.
authors: Heather
authors: H
authors: Herd
authors: Nicole
authors: N
authors: Daum
authors: Arwyn T
authors: AT
authors: Jones
authors: Hanno
authors: H
authors: Huwer
authors: Hamidreza
authors: H
authors: Ghandehari
authors: Claus-Michael
authors: CM
authors: Lehr
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity; D001693:Biological Transport, Active; D002460:Cell Line; D003911:Dextrans / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004705:Endocytosis; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008422:Materials Testing; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity; D013499:Surface Properties; D014168:Transferrin / Q000493:pharmacokinetics
chemical_list: D001672:Biocompatible Materials; D003911:Dextrans; D014168:Transferrin; D012822:Silicon Dioxide; D019869:Phosphatidylinositol 3-Kinases
references: Pharm Res. 2009 Jan;26(1):244-9
references: 18548338
references: J Cell Mol Med. 2007 Jul-Aug;11(4):670-84
references: 17760832
references: J Gen Virol. 2011 Jul;92(Pt 7):1688-1697
references: 21450945
references: Bioinformatics. 2006 Dec 1;22(23):2926-33
references: 17000751
references: Blood. 2002 Feb 1;99(3):912-22
references: 11806994
references: Diabetes Care. 1984 May-Jun;7 Suppl 1:35-41
references: 6145551
references: Pharmacol Rev. 2006 Mar;58(1):32-45
references: 16507881
references: Biochem J. 2004 Jan 1;377(Pt 1):159-69
references: 14505488
references: Aging (Albany NY). 2009 Jun 03;1(6):515-28
references: 20157535
references: Expert Opin Drug Deliv. 2010 Aug;7(8):895-913
references: 20629604
references: Bioconjug Chem. 2004 Jul-Aug;15(4):774-82
references: 15264864
references: Respir Res. 2010 Sep 15;11:124
references: 20843333
references: Nat Mater. 2009 Jul;8(7):543-57
references: 19525947
references: Cell. 2004 Sep 17;118(6):767-80
references: 15369675
references: Acc Chem Res. 2013 Mar 19;46(3):743-9
references: 22786674
references: Macromol Rapid Commun. 2010 Jan 18;31(2):142-8
references: 21590886
references: ACS Nano. 2010 May 25;4(5):2490-3
references: 20496953
references: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11613-8
references: 18697944
references: Biochem J. 1984 Feb 1;217(3):649-58
references: 6231917
references: J Cell Biol. 1993 Dec;123(5):1107-17
references: 8245121
references: J Biol Chem. 1999 Jan 15;274(3):1240-7
references: 9880492
references: J Control Release. 2011 Jul 15;153(1):40-8
references: 21342660
references: Mol Ther. 2010 Mar;18(3):561-9
references: 20010917
references: Annu Rev Biochem. 2009;78:857-902
references: 19317650
references: Nano Lett. 2011 Dec 14;11(12):5391-5
references: 22047641
references: Adv Drug Deliv Rev. 2003 Nov 14;55(11):1353-7
references: 14597135
references: Traffic. 2003 Nov;4(11):724-38
references: 14617356
references: J R Soc Interface. 2010 Aug 6;7 Suppl 4:S403-10
references: 20504803
references: Cell Res. 2010 Mar;20(3):256-75
references: 20125123
references: Pharm Res. 2008 Aug;25(8):1815-21
references: 18373181
references: Biochem Soc Trans. 2009 Feb;37(Pt 1):232-6
references: 19143638
references: Biomaterials. 2007 Jun;28(18):2915-22
references: 17363051
references: Pharm Res. 2008 Dec;25(12):2845-52
references: 18592353
references: Nano Lett. 2007 Jun;7(6):1542-50
references: 17465586
references: PLoS One. 2010 Jun 08;5(6):e11004
references: 20543983
references: ACS Nano. 2011 Jun 28;5(6):4434-47
references: 21563770
references: J Cell Biol. 1996 Dec;135(5):1249-60
references: 8947549
references: Biophys J. 2008 May 15;94(10):3790-7
references: 18234813
references: Haematol Blood Transfus. 1985;29:511-3
references: 4029739
references: J Cell Biol. 2006 Feb 27;172(5):719-31
references: 16505167
references: PLoS One. 2010 Apr 06;5(4):e10051
references: 20386614
references: ACS Nano. 2012 Feb 28;6(2):1565-77
references: 22214244
references: Methods Mol Biol. 2012;806:31-42
references: 22057443
references: J Biol Chem. 2001 Jul 13;276(28):26164-70
references: 11316799
references: J Appl Physiol Respir Environ Exerc Physiol. 1981 Mar;50(3):621-9
references: 7195895
references: Mol Ther. 2008 Aug;16(8):1450-8
references: 18560419
references: J Cell Sci. 1980 Oct;45:59-71
references: 7462349
references: Nano Lett. 2006 Apr;6(4):662-8
references: 16608261