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Quantitative analysis of gold and carbon nanoparticles in mammalian cells by flow cytometry light scattering

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Abstract

Nanoparticle-based applications for diagnostics and therapeutics have been extensively studied. These applications require a profound understanding of the fate of nanoparticles (NPs) in cellular environments. However, until now, few analytical methods are available and most of them rely on fluorescent properties or special elements of NPs; therefore, for NPs without observable optical properties or special elements, the existing methods are hardly applicable. In this study, we introduce a flow cytometry light scattering (FCLS)-based approach that quantifies in situ NPs accurately in mammalian cells. Continuous cells of heterogeneous human epithelial colorectal adenocarcinoma (Caco-2 cells), mouse peritoneal macrophages (MPM), and human adenocarcinomic alveolar basal epithelia (A549 cells) were cultured with NPs with certain concentrations and size. The intensity of the flow cytometric side scattered light, which indicates the quantity of NPs in the cells, was analyzed. The result shows an accurate size- and dose-dependent uptake of Au NPs (5, 30, 250 nm) in Caco-2 cells. The size- and dose- dependence of Au NPs (5, 30, 250 nm) and carbon NPs (50, 500 nm) in cells was validated by transmission electron microscope (TEM). This paper demonstrates the great potential of flow cytometry light scattering in the quantitative study of the size and dose effect on in situ metallic or non-metallic NPs in mammalian cells.

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References

  • Albanese A, Tang PS, Chan WC (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14:1–16. doi:10.1146/annurev-bioeng-071811-150124

    Article  Google Scholar 

  • Bianco A (2004) Carbon nanotubes for the delivery of therapeutic molecules. Expert opinion on drug delivery 1:57–65. doi:10.1517/17425247.1.1.57

    Article  Google Scholar 

  • Bianco A, Kostarelos K, Partidos CD, Prato M (2005a) Biomedical applications of functionalised carbon nanotubes. Chem Commun 571–577 doi:10.1039/b410943k

  • Bianco A, Kostarelos K, Prato M (2005b) Applications of carbon nanotubes in drug delivery. Curr Opin Chem Biol 9:674–679. doi:10.1016/j.cbpa.2005.10.005

    Article  Google Scholar 

  • Cheng Y, Samia AC, Meyers JD, Panagopoulos I, Fei B, Burda C (2008) Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer. J Am Chem Soc 130:10643–10647. doi:10.1021/ja801631c

  • Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668. doi:10.1021/nl052396o

    Article  Google Scholar 

  • Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA (2012) The golden age: gold nanoparticles for biomedicine. Chem Soc Rev 41:2740–2779. doi:10.1039/c1cs15237h

    Article  Google Scholar 

  • Dykman LA, Khlebtsov NG (2013) Uptake of engineered gold nanoparticles into mammalian cells. Chem Rev 114:1258–1288

    Article  Google Scholar 

  • Hu M, Ling J, Lin H, Chen J (2004) Use of Caco-2 Cell Monolayers to study drug absorption and metabolism. In: Yan Z, Caldwell G (eds) Optimization in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, pp 19–35. doi:10.1385/1-59259-800-5:019

  • Jiang W, Kim BY, Rutka JT, Chan WC (2008) Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol 3:145–150. doi:10.1038/nnano.2008.30

    Article  Google Scholar 

  • Jones LM, Sperry JB, Carroll JA, Gross ML (2011) Fast photochemical oxidation of proteins for epitope mapping. Anal Chem 83:7657–7661. doi:10.1021/ac2007366

    Article  Google Scholar 

  • Kuhn DA, Vanhecke D, Michen B, Blank F, Gehr P, Petri-Fink A, Rothen-Rutishauser B (2014) Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages. Beilstein journal of nanotechnology 5:1625–1636. doi:10.3762/bjnano.5.174

    Article  Google Scholar 

  • Lai Y et al (2008) Comparison of in vitro nanoparticles uptake in various cell lines and in vivo pulmonary cellular transport in Intratracheally dosed rat model. Nanoscale Res Lett 3:321–329. doi:10.1007/s11671-008-9160-2

    Article  Google Scholar 

  • Lunov O et al (2011) Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano 5:1657–1669

    Article  Google Scholar 

  • Miller SE et al (2015) CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. Dev Cell 33:163–175. doi:10.1016/j.devcel.2015.03.002

    Article  Google Scholar 

  • Muhlfeld C, Rothen-Rutishauser B, Vanhecke D, Blank F, Gehr P, Ochs M (2007) Visualization and quantitative analysis of nanoparticles in the respiratory tract by transmission electron microscopy. Particle and fibre toxicology 4:11. doi:10.1186/1743-8977-4-11

    Article  Google Scholar 

  • Nel AE et al (2015) Where are we heading in nanotechnology environmental health and safety and materials characterization? ACS Nano 9:5627–5630. doi:10.1021/acsnano.5b03496

    Article  Google Scholar 

  • Ng CT, Tang FM, Li JJ, Ong C, Yung LL, Bay BH (2015) Clathrin-mediated endocytosis of gold nanoparticles in vitro. Anat Rec 298:418–427. doi:10.1002/ar.23051

    Article  Google Scholar 

  • Oh WK, Yoon H, Jang J (2010) Size control of magnetic carbon nanoparticles for drug delivery. Biomaterials 31:1342–1348. doi:10.1016/j.biomaterials.2009.10.018

    Article  Google Scholar 

  • Ortega RA, Barham WJ, Kumar B, Tikhomirov O, McFadden ID, Yull FE, Giorgio TD (2015) Biocompatible mannosylated endosomal-escape nanoparticles enhance selective delivery of short nucleotide sequences to tumor associated macrophages. Nanoscale 7:500–510

    Article  Google Scholar 

  • Picot J, Guerin CL, Le Van Kim C, Boulanger CM (2012) Flow cytometry: retrospective, fundamentals and recent instrumentation. Cytotechnology 64:109–130. doi:10.1007/s10616-011-9415-0

    Article  Google Scholar 

  • Simovic S, Song Y, Nann T, Desai TA (2015) Intestinal absorption of fluorescently labeled nanoparticles. Nanomedicine : nanotechnology, biology, and medicine. doi:10.1016/j.nano.2015.02.016

    Google Scholar 

  • Suzuki H, Toyooka T, Ibuki Y (2007) Simple and easy method to evaluate uptake potential of nanoparticles in mammalian cells using a flow cytometric light scatter analysis. Environmental science & technology 41:3018–3024

    Article  Google Scholar 

  • Syed A, Chan WC (2015) How nanoparticles interact with cancer cells. Cancer Treat Res 166:227–244. doi:10.1007/978-3-319-16555-4_10

    Article  Google Scholar 

  • Thakor AS, Jokerst J, Zavaleta C, Massoud TF, Gambhir SS (2011) Gold nanoparticles: a revival in precious metal administration to patients. Nano Lett 11:4029–4036. doi:10.1021/nl202559p

    Article  Google Scholar 

  • Yan A, Lau BW, Weissman BS, Külaots I, Yang NY, Kane AB, Hurt RH (2006) Biocompatible, hydrophilic, supramolecular carbon nanoparticles for cell delivery. Adv Mater 18:2373–2378

    Article  Google Scholar 

  • Yang Z, Zhang Y, Yang Y, Sun L, Han D, Li H, Wang C (2010) Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine : nanotechnology, biology, and medicine 6:427–441. doi:10.1016/j.nano.2009.11.007

    Google Scholar 

  • Zhang S, Gao H, Bao G (2015) Physical principles of nanoparticle cellular endocytosis. ACS Nano. doi:10.1021/acsnano.5b03184

    Google Scholar 

  • Zhao Y, Xing G, Chai Z (2008) Nanotoxicology: are carbon nanotubes safe? Nat Nanotechnol 3:191–192. doi:10.1038/nnano.2008.77

    Article  Google Scholar 

  • Zhao F, Meng H, Yan L, Wang B, Zhao Y (2014) Nanosurface chemistry and dose govern the bioaccumulation and toxicity of carbon nanotubes, metal nanomaterials and quantum dots in vivo. Science Bulletin 60:3–20. doi:10.1007/s11434-014-0700-0

    Article  Google Scholar 

  • Zucker RM, Daniel KM (2012) Detection of TiO2 nanoparticles in cells by flow cytometry. Methods Mol Biol 906:497–509. doi:10.1007/978-1-61779-953-2_40

    Google Scholar 

  • Zucker RM, Massaro EJ, Sanders KM, Degn LL, Boyes WK (2010) Detection of TiO2 nanoparticles in cells by flow cytometry. Cytometry Part A : the journal of the International Society for Analytical Cytology 77:677–685. doi:10.1002/cyto.a.20927

    Article  Google Scholar 

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Acknowledgments

This study was funded by the scientific research foundation of graduate school of Nanjing University (2015CL12).

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Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, People’s Republic of China

    Gang Zhou, Tongguo Shi, Jingjing Gan, Zhenzhen Wang & Junfeng Zhang

  2. Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210093, People’s Republic of China

    Naicheng Liu & Zhenheng Wang

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  1. Gang Zhou
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  2. Naicheng Liu
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  3. Zhenheng Wang
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  4. Tongguo Shi
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  5. Jingjing Gan
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  6. Zhenzhen Wang
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  7. Junfeng Zhang
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Correspondence to Junfeng Zhang.

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Zhou, G., Liu, N., Wang, Z. et al. Quantitative analysis of gold and carbon nanoparticles in mammalian cells by flow cytometry light scattering. J Nanopart Res 19, 78 (2017). https://doi.org/10.1007/s11051-017-3787-9

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