title: High resolution characterization of engineered nanomaterial dispersions in complex media using tunable resistive pulse sensing technology.
abstract: In vitro toxicity assessment of engineered nanomaterials (ENM), the most common testing platform for ENM, requires prior ENM dispersion, stabilization, and characterization in cell culture media. Dispersion inefficiencies and active aggregation of particles often result in polydisperse and multimodal particle size distributions. Accurate characterization of important properties of such polydisperse distributions (size distribution, effective density, charge, mobility, aggregation kinetics, etc.) is critical for understanding differences in the effective dose delivered to cells as a function of time and dispersion conditions, as well as for nano-bio interactions. Here we have investigated the utility of tunable nanopore resistive pulse sensing (TRPS) technology for characterization of four industry relevant ENMs (oxidized single-walled carbon nanohorns, carbon black, cerium oxide and nickel nanoparticles) in cell culture media containing serum. Harvard dispersion and dosimetry platform was used for preparing ENM dispersions and estimating delivered dose to cells based on dispersion characterization input from dynamic light scattering (DLS) and TRPS. The slopes of cell death vs administered and delivered ENM dose were then derived and compared. We investigated the impact of serum protein content, ENM concentration, and cell medium on the size distributions. The TRPS technology offers higher resolution and sensitivity compared to DLS and unique insights into ENM size distribution and concentration, as well as particle behavior and morphology in complex media. The in vitro dose-response slopes changed significantly for certain nanomaterials when delivered dose to cells was taken into consideration, highlighting the importance of accurate dispersion and dosimetry in in vitro nanotoxicology.
authors.affiliation: Biomedical Engineering and Biotechnology Program; ‡Department of Work Environment, College of Health Sciences, ¥Department of Biological Sciences, §Department of Plastics Engineering; ⊥Center for High-Rate Nanomanufacturing, University of Massachusetts Lowell , Lowell, Massachusetts 01854, United States.
authors.forename: Anoop K
authors.initials: AK
authors.lastname: Pal
authors.forename: Iraj
authors.initials: I
authors.lastname: Aalaei
authors.forename: Suresh
authors.initials: S
authors.lastname: Gadde
authors.forename: Peter
authors.initials: P
authors.lastname: Gaines
authors.forename: Daniel
authors.initials: D
authors.lastname: Schmidt
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
authors.forename: Dhimiter
authors.initials: D
authors.lastname: Bello
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004738:Engineering; D006801:Humans; D058608:Nanopores; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity; D036103:Nanotechnology / Q000379:methods*
keywords: DLS; TRPS; cytotoxicity; effective density; nanomaterial; size distribution
references.citation: ACS Sustain Chem Eng. 2014 Jul 7;2(7):1681-1690
references.pmid: 25068097
references.citation: Dose Response. 2012;10(3):308-30
references.pmid: 22942866
references.citation: J Phys Chem C Nanomater Interfaces. 2012 Apr 19;116(15):8554-8561
references.pmid: 22942926
references.citation: Langmuir. 2004 Aug 3;20(16):6940-5
references.pmid: 15274607
references.citation: Nanotoxicology. 2011 Dec;5(4):711-29
references.pmid: 21073401
references.citation: Anal Bioanal Chem. 2010 Feb;396(3):953-61
references.pmid: 19756533
references.citation: Environ Sci Process Impacts. 2013 Jan;15(1):23-38
references.pmid: 24592425
references.citation: Part Fibre Toxicol. 2008 Nov 06;5:14
references.pmid: 18990217
references.citation: Environ Health Toxicol. 2012;27:e2012015
references.pmid: 23106037
references.citation: Toxicol Sci. 2008 Feb;101(2):183-5
references.pmid: 18300382
references.citation: ACS Nano. 2012 Aug 28;6(8):6990-7
references.pmid: 22809054
references.citation: Anal Chem. 2003 May 15;75(10):2399-406
references.pmid: 12918983
references.citation: ACS Nano. 2011 Sep 27;5(9):7284-95
references.pmid: 21851096
references.citation: Part Fibre Toxicol. 2005 Oct 06;2:8
references.pmid: 16209704
references.citation: Nanotoxicology. 2013 Dec;7(8):1338-50
references.pmid: 23061914
references.citation: Langmuir. 2013 Sep 10;29(36):11385-95
references.pmid: 23978039
references.citation: Nanotoxicology. 2013 Jun;7(4):389-401
references.pmid: 22397515
references.citation: Nat Commun. 2014 Mar 28;5:3514
references.pmid: 24675174
references.citation: Nat Nanotechnol. 2007 Aug;2(8):469-78
references.pmid: 18654343
references.citation: J Agric Food Chem. 2008 Sep 24;56(18):8231-47
references.pmid: 18759445
references.citation: Nanotoxicology. 2014 Aug;8 Suppl 1:216-25
references.pmid: 24479615
references.citation: Small. 2012 Aug 6;8(15):2436-44
references.pmid: 22570187
references.citation: Chem Res Toxicol. 2009 Mar 16;22(3):543-53
references.pmid: 19216582
references.citation: Toxicol Sci. 2006 Apr;90(2):296-303
references.pmid: 16407094
references.citation: Toxicol Sci. 2005 Oct;87(2):316-21
references.pmid: 16049265
references.citation: Part Fibre Toxicol. 2006 Aug 14;3:11
references.pmid: 16907977
references.citation: Environ Sci Technol. 2010 Oct 1;44(19):7309-14
references.pmid: 20536146
references.citation: Integr Biol (Camb). 2013 Jan;5(1):66-73
references.pmid: 22772974
references.citation: J Colloid Interface Sci. 2013 Sep 1;405:322-30
references.pmid: 23759321
references.citation: Annu Rev Pharmacol Toxicol. 2010;50:63-88
references.pmid: 20055698
references.citation: J Phys Chem C Nanomater Interfaces. 2011 Feb 24;115(7):2999-3004
references.pmid: 27347278
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4930-4
references.pmid: 16549762
references.citation: Small. 2013 May 27;9(9-10):1853-65
references.pmid: 23423873
references.citation: Environ Health Perspect. 2005 Jul;113(7):823-39
references.pmid: 16002369
references.citation: Part Fibre Toxicol. 2014 May 01;11:20
references.pmid: 24885440
references.citation: Nanotoxicology. 2013 Jun;7(4):417-31
references.pmid: 22393878
references.citation: Biophys J. 1973 Mar;13(3):265-80
references.pmid: 4697237
references.citation: Toxicol Sci. 2008 Feb;101(2):239-53
references.pmid: 17872897
references.citation: J Colloid Interface Sci. 2010 Apr 15;344(2):528-32
references.pmid: 20138293
references.citation: Part Fibre Toxicol. 2010 Nov 30;7(1):36
references.pmid: 21118529
references.citation: Annu Rev Biomed Eng. 2012;14:1-16
references.pmid: 22524388
references.citation: J Am Chem Soc. 2010 Apr 28;132(16):5761-8
references.pmid: 20356039
references.citation: Part Fibre Toxicol. 2013 Aug 22;10:42
references.pmid: 23968360
references.citation: Nat Mater. 2009 Jul;8(7):543-57
references.pmid: 19525947
references.citation: Nanomedicine. 2009 Jun;5(2):106-17
references.pmid: 19071065