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Gold nanoparticles: uptake in human mast cells and effect on cell viability, inflammatory mediators, and proliferation

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Abstract

Background

Gold nanoparticles (AuNPs) have potential for a wide range of applications as therapeutic and diagnostic agents. Since they have a high probability of interacting with human immune cells, cytotoxicity studies must be conducted. The investigation of AuNP/immune cell interaction has mainly focused on macrophages and dendritic cells, along with some other cell lineages. Scarce information is available regarding the effect of AuNPs on mast cells, which are abundant in the skin, mucosa, and perivascular space.

Objective

To examine the uptake of AuNPs by HMC-1 human mast cells and the resulting effect on cell viability, pro-inflammatory mediators production, and proliferation.

Results

With AuNPs treatment, the viability of HMC-1 cells decreased slightly (never less than 95%) during the first 4 h, but no changes were detected in the proliferation rate at any time. Increasing concentrations of AuNPs produced greater cell granularity (uptake). CLSM images exhibited AuNPs clusters in the cell cytoplasm. TNF-α and ROS production was not stimulated by AuNPs treatment at any concentration/time.

Conclusion

Internalization of AuNPs into HMC-1 cells was demonstrated in an in vitro model, without showing cytotoxic effects or induction of pro-inflammatory mediators at any concentration tested.

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References

  • Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE (2009) Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev 61:428–437

    Article  CAS  Google Scholar 

  • Aldossari AA, Shannahan JH, Podila R, Brown JM (2015) Influence of physicochemical properties of silver nanoparticles on mast cell activation and degranulation. Toxicol Vitr 29:195–203

    Article  CAS  Google Scholar 

  • Alsaleh NB, Brown JM (2018) Immune responses to engineered nanomaterials: current understanding and challenges. Curr Opin Toxicol 10:8–14

    Article  Google Scholar 

  • Ansari SA et al. (2019) Gold nanoparticles synthesized with Smilax glabra rhizome modulates the anti-obesity parameters in high-fat diet and streptozotocin induced obese diabetes rat model. J Photochem Photobiol B Biol 201:111643.

  • BioLegend (n.d.) 7-AAD Viability Staining Solution. BioLegend. https://www.biolegend.com/en-us/products/7-aad-viability-staining-solution-1649

  • Boisselier E, Astruc D (2009) Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 38:1759–1782

    Article  CAS  Google Scholar 

  • Boyd RD, Pichaimuthu SK, Cuenat A (2011) New approach to inter-technique comparisons for nanoparticle size measurements; using atomic force microscopy, nanoparticle tracking analysis and dynamic light scattering. Colloids Surfaces A Physicochem Eng Asp 387:35–42

    Article  CAS  Google Scholar 

  • Campillo-Navarro M et al (2014) Mast cells in lung homeostasis: beyond type I hypersensitivity. Curr Respir Med Rev 10:115–123

    Article  CAS  Google Scholar 

  • Carnovale C, Bryant G, Shukla R, Bansal V (2016) Size, shape and surface chemistry of nano-gold dictate its cellular interactions, uptake and toxicity. Prog Mater Sci 83:152–190

    Article  CAS  Google Scholar 

  • Chen H et al (2018) Gold nanoparticles improve metabolic profile of mice fed a high-fat diet. J Nanobiotechnology 16:1–12

    Article  Google Scholar 

  • Chithrani BD, Chan WCW (2007) Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett 7:1542–1550

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Cho WS et al (2009) Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. Toxicol Appl Pharmacol 236:16–24

    Article  CAS  Google Scholar 

  • Cleyrat C et al (2013) The architectural relationship of components controlling mast cell endocytosis. J Cell Sci 126:4913–4925

    CAS  PubMed  PubMed Central  Google Scholar 

  • Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327

    Article  CAS  Google Scholar 

  • Cui W et al. (2012) Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. Nanomed Nanotechnol Biol Med 8:46–53.

  • Devika Chithrani B, Ghazani AA, Chan WCW (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 6: 662–668.

  • Dey AK et al. (2021) Impact of Gold Nanoparticles on the Functions of Macrophages and Dendritic Cells. Cells 10.

  • Dobrovolskaia MA, McNeil SE (2007) Immunological properties of engineered nanomaterials. Nat Nanotechnol 2:469–478

    Article  CAS  Google Scholar 

  • Du S et al. Aggregation and adhesion of gold nanoparticles in phosphate buffered saline. J Nanoparticle Res. 14, (2012).

  • Duguay BA, Lu L, Arizmendi N, Unsworth LD, Kulka M (2020) The possible uses and challenges of nanomaterials in mast cell research. J Immunol 204:2021–2032

    Article  CAS  Google Scholar 

  • Dykman L, Khlebtsov N (2012) Gold nanoparticles in biomedical applications: recent advances and perspectives. Chem Soc Rev 41:2256–2282

    Article  CAS  Google Scholar 

  • Dykman LA, Khlebtsov NG (2017) Immunological properties of gold nanoparticles. Chem Sci 8:1719–1735

    Article  CAS  Google Scholar 

  • Gallego-Urrea JA, Tuoriniemi J, Hassellöv M (2011) Applications of particle-tracking analysis to the determination of size distributions and concentrations of nanoparticles in environmental, biological and food samples. TrAC—Trends Anal Chem 30:473–483

    Article  CAS  Google Scholar 

  • Khademi S et al (2018) Evaluation of size, morphology, concentration, and surface effect of gold nanoparticles on X-ray attenuation in computed tomography. Phys Medica 45:127–133

    Article  Google Scholar 

  • Kim JY, Ro JY (2005) Signal pathway of cytokines produced by reactive oxygen species generated from phorbol myristate acetate-stimulated HMC-1 cells. Scand J Immunol 62:25–35

    Article  CAS  Google Scholar 

  • Klippstein R, Fernandez-Montesinos R, M, P, P, A, Pozo D (2010) Silver Nanoparticles Interactions with the Immune System: Implications for Health and Disease. In: Silver Nanoparticles. InTech.

  • Kumar D, Saini N, Jain N, Sareen R, Pandit V (2013) Gold nanoparticles: an era in bionanotechnology. Expert Opin Drug Deliv 10:397–409

    Article  CAS  Google Scholar 

  • Lebedová J, Hedberg YS, Odnevall Wallinder I, Karlsson HL (2018) Size-dependent genotoxicity of silver, gold and platinum nanoparticles studied using the mini-gel comet assay and micronucleus scoring with flow cytometry. Mutagenesis 33:77–85.

  • Logozzi M et al. (2019) Human primary macrophages scavenge AuNPs and eliminate it through exosomes. A natural shuttling for nanomaterials. Eur J Pharm Biopharm 137:23–36.

  • Marquis BJ, McFarland AD, Braun KL, Haynes CL (2008) Dynamic measurement of altered chemical messenger secretion after cellular uptake of nanoparticles using carbon-fiber microelectrode amperometry. Anal Chem 80:3431–3437

    Article  CAS  Google Scholar 

  • Marshall JS (2004) Mast-cell responses to pathogens. Nat Rev Immunol 4:787–799

    Article  CAS  Google Scholar 

  • Mateo D, Morales P, Ávalos A, Haza AI (2014) Oxidative stress contributes to gold nanoparticle-induced cytotoxicity in human tumor cells. Toxicol Mech Methods 24:161–172

    Article  CAS  Google Scholar 

  • Maurer-Jones MA, Lin YS, Haynes CL (2010) Functional assessment of metal oxide nanoparticle toxicity in immune cells. ACS Nano 4:3363–3373

    Article  CAS  Google Scholar 

  • Mukherjee P et al (2005) Antiangiogenic properties of gold nanoparticles. Clin Cancer Res 11:3530–3534

    Article  CAS  Google Scholar 

  • Pissuwan D, Valenzuela SM, Cortie MB (2006) Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends Biotechnol 24:62–67

    Article  CAS  Google Scholar 

  • Prabha S, Arya G, Chandra R, Ahmed B, Nimesh S (2016) Effect of size on biological properties of nanoparticles employed in gene delivery. Artif Cells Nanomed Biotechnol 44:83–91.

  • Sahay G, Alakhova DY, Kabanov AV (2010) Endocytosis of nanomedicines. J Control Release 145:182–195

    Article  CAS  Google Scholar 

  • Salatin S, Maleki Dizaj S, Yari Khosroushahi A (2015) Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int 39:881–890.

  • Sapsford KE et al (2013) Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology. Chem Rev 113:1904–2074

    Article  CAS  Google Scholar 

  • Singh P et al. (2018) Gold nanoparticles in diagnostics and therapeutics for human cancer. Int J Mol Sci 19.

  • Sundström M et al (2003) Functional and phenotypic studies of two variants of a human mast cell line with a distinct set of mutations in the c-kit proto-oncogene. Immunology 108:89–97

    Article  Google Scholar 

  • Sundström C et al (2006) Phenotypic characterization of the human mast-cell line HMC-1. Scand J Immunol 39:489–498

    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. Environ Sci Technol 41:3018–3024

    Article  CAS  Google Scholar 

  • Theoharides TC, Conti P (2004) Mast cells: The JEKYLL and HYDE of tumor growth. Trends Immunol 25:235–241

    Article  CAS  Google Scholar 

  • Thermo Fisher Cientific (n.d.-b) CM-H2DCFDA (General Oxidative Stress Indicator). https://www.thermofisher.com/order/catalog/product/C6827#/C6827

  • Thermo Fisher Cientific. (n.d.-a). CellTrace TM CFSE Cell Proliferation Kit - For Flow Cytometry. https://www.thermofisher.com/order/catalog/product/C34554

  • Toma HE, Zamarion VM, Toma SH, Araki K (2010) The coordination chemistry at gold nanoparticles. J Braz Chem Soc 21:1158–1176

    Article  CAS  Google Scholar 

  • Tomic S et al (2014) Size-dependent effects of gold nanoparticles uptake on maturation and antitumor functions of human dendritic cells in vitro. PLoS ONE 9:96584

    Article  Google Scholar 

  • Trautmann A, Krohne G, Brocker EB, Klein CE (1998) Human mast cells augment fibroblast proliferation by heterotypic cell-cell adhesion and action of IL-4. J Immunol 160:5053–5057

    CAS  PubMed  Google Scholar 

  • Yamaki K, Yoshino S (2009) Comparison of inhibitory activities of zinc oxide ultrafine and fine particulates on IgE-induced mast cell activation. Biometals 22:1031–1040

    Article  CAS  Google Scholar 

  • Yasinska IM et al (2019) Targeting of basophil and mast cell pro-allergic reactivity using functionalised gold nanoparticles. Front Pharmacol 10:1–7

    Article  Google Scholar 

  • Youhannayee M et al (2019) Physical characterization and uptake of iron oxide nanoparticles of different prostate cancer cells. J Magn Magn Mater 473:205–214

    Article  CAS  Google Scholar 

  • Zamora-Justo JA et al (2019) Polyethylene glycol-coated gold nanoparticles as DNA and atorvastatin delivery systems and cytotoxicity evaluation. J Nanomater 2019:1–11

    Article  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Guillermo Pérez-Dimas and Luis Gilberto Pérez-Blas for technical assistance in cell culture, to Dr. Rommel Chacón-Salinas for providing HMC-1 cells, and to the core faculty of flow cytometry of the ESM-IPN under the direction of Dr. Marycarmen Godínez-Victoria. We greatly appreciate the Hematopathology Lab of the ENCB-IPN, Dr. Elba Reyes-Maldonado, Dr. Ruth Angélica Lezama-Palacios, M.S. Erika Rosales-Cruz, and the CNMN-IPN. RAG-C acknowledges the Consejo Nacional de Ciencia y Tecnología (CONACyT) for the PhD scholarship. OR-C acknowledges the Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (SIP-20210826) for the funding granted. AM-D acknowledges the Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (SIP-20196318, SIP-20200845) and the Secretaría de Educación, Ciencia, Tecnología e Innovación de la Ciudad de México (SECTEI/271/2019) for the funding granted.

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Contributions

Conceptualization: RAG-C, OR-C and AM-D; experimental design: RAG-C, OR-C and RF-M; experimental execution: RAG-C; data acquisition and processing: RAG-C; formal analysis: RAG-C and OR-C; funding acquisition: AM-D and OR-C; project administration: AM-D and OR-C; writing original draft: RAG-C and OR-C; writing review: AM-D, OR-C and RF-M.

Corresponding author

Correspondence to Ramón A. Gutiérrez-Calleja.

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RAG-C declares that he has not conflict of interest. ORC-C declares that he has not conflict of interest. RF-M declares that he has not conflict of interest. AM-D declares that he has not conflict of interest.

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Gutiérrez-Calleja, R.A., Rodríguez-Cortés, O., Flores-Mejía, R. et al. Gold nanoparticles: uptake in human mast cells and effect on cell viability, inflammatory mediators, and proliferation. Mol. Cell. Toxicol. 17, 439–452 (2021). https://doi.org/10.1007/s13273-021-00152-7

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