Skip to main content
Log in

Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702 cells

  • Original Research
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Silver nanoparticles (AgNPs) are being used widely and increasingly in various products and medical supplies due to their antibacterial activity. However, little is known about the impacts of the AgNPs. Herein, The primary purpose of this study was to investigate the cytotoxic effect of AgNPs in the human liver cell line (HL-7702). The water-soluble α-Methoxy-poly (ethylene glycol)-ω-mercapto (mPEG-SH)-coated AgNPs (40 nm) were synthesized, which showed superior stabilization and uniform dispersion in culture medium. The effect of mPEG-SH-coated silver nanoparticles on cell viability, leakage of lactate dehydrogenase (LDH), oxidative stress, mitochondrial membrane potential (MMP), and cell cycle was evaluated after the cells were treated with nanoparticles. The results showed that the coated AgNPs could be taken up by cells, decreased cell viability in dose- and time-dependent manners at dosage levels between 6.25 and 100.00 μg/mL, caused membrane damage (LDH leakage), and decreased the activities of superoxide dismutase and glutathione peroxides. The level of malondialdehyde, an end product of lipid peroxidation, was also increased in AgNPs-exposed cells. Moreover, flow cytometric analysis showed that AgNP exposure decrease MMP and cause G2/M phase arrest. Thus, our data suggest that mPEG-SH-coated AgNPs have the potential toxicity that is associated with oxidative stress, apoptosis, and DNA damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AgNPs:

Silver nanoparticles

FBS:

Fetal bovine serum

FCM:

Flow cytometer

GPx:

Glutathione peroxides

LDH:

Lactate dehydrogenase

mPEG-SH:

α-Methoxy-poly (ethylene glycol)-ω-mercapto

MMP:

Mitochondrial membrane potential

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MDA:

Malondialdehyde

PI:

Propidium iodide

PBS:

Phosphate-buffered saline

Rh-123:

Rhodamine 123

SOD:

Superoxide dismutase

TEM:

Transmission electron microscope

TBARS:

Thiobarbituric acid reactive substance

References

  • Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, et al. DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharmacol. 2008;233:404–10.

    Article  PubMed  CAS  Google Scholar 

  • Asharani PV, Wu YL, Gong ZY, Valiyaveettil S. Toxicity of silver nanoparticles in zebrafish models. Nanotechnology. 2008;19:255102.

    Article  PubMed  CAS  Google Scholar 

  • AshaRani PV, Mun GLK, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009;3:279–90.

    Article  PubMed  CAS  Google Scholar 

  • Baracca A, Sgarbi G, Solaini G, Lenaz G. Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F0 during ATP synthesis. Biochim Biophys Acta. 2003;1606:137–46.

    Article  PubMed  CAS  Google Scholar 

  • Bose B, Motiwale L, Rao KV. DNA damage and G2/M arrest in Syrian hamster embryo cells during Malachite green exposure are associated with elevated phosphorylation of ERK1 and JNK1. Cancer Lett. 2005;230:260–70.

    Article  PubMed  CAS  Google Scholar 

  • Brutel de la Rivière A, Dossche KM, Birnbaum DE, Hacker R. First clinical experience with a mechanical valve with silver coating. J Heart Valve Dis. 2000;9:123–9.

    PubMed  CAS  Google Scholar 

  • Cha K, Hong HW, Choi YG, Lee MJ, Park JH, Chae HK, et al. Comparison of acute responses of mice livers to short-term exposure to nano-sized or micro-sized silver particles. Biotechnol Lett. 2008;30:1893–9.

    Article  PubMed  CAS  Google Scholar 

  • Chau CF, Wu SH, Yen GC. The development of regulations for food nanotechnology. Trends Food Sci Tech. 2007;18:269–80.

    Article  CAS  Google Scholar 

  • Chen X, Schluesener HJ. Nanosilver: a nanoproduct in medical application. Toxicol Lett. 2008;176:1–12.

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Han CM, Lin XW, Tang ZJ, Su SJ. Effect of silver nanoparticle dressing on second degree burn wound. Zhonghua Wai Ke Za Zhi. 2006;44:50–2.

    PubMed  Google Scholar 

  • Cheng DC, Yang J, Zhao YL. Antibacterial materials of silver nanoparticles application in medical appliances and appliances for daily use. Chin Med Equip J. 2004;25:26–32.

    Google Scholar 

  • Choi JE, Kim S, Ahn JH, Youn P, Kang JS, Park K, et al. Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish. Aqua Toxicol. 2010;100:151–9.

    Article  CAS  Google Scholar 

  • Cohen MS, Stern JM, Vanni AJ, Kelley RS, Baumgart E, Field D, et al. In vitro analysis of a nanocrystalline silver-coated surgical mesh. Surg Infect. 2007;8:397–404.

    Article  Google Scholar 

  • Cuddihy AR, O’Connell MJ. Cell-cycle responses to DNA damage in G2. Int Rev Cytol. 2003;222:99–140.

    Article  PubMed  Google Scholar 

  • Dubas ST, Pimpan V. Humic acid assisted synthesis of silver nanoparticles and its application to herbicide detection. Mater Lett. 2008;62:2661–3.

    Article  CAS  Google Scholar 

  • Foldbjerg R, Olesen P, Hougaard M, Dang DA, Hoffmann H, Autrup H. PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes. Toxicol Lett. 2009;190:156–62.

    Article  PubMed  CAS  Google Scholar 

  • Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–9.

    Article  PubMed  CAS  Google Scholar 

  • Hsin YH, Chen CF, Huang S, Shih TS, Lai PS, Chueh PJ. The apoptotic effect of nanosilver is mediated by a ROS-and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett. 2008;179:130–9.

    Article  PubMed  CAS  Google Scholar 

  • Hussain SM, Hess K, Gearhart JM, Geiss KT, Schlager JJ. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol Vitro. 2005;19:975–83.

    Article  CAS  Google Scholar 

  • Janardhanan R, Karuppaiah M, Hebalkar N, Rao TN. Synthesis and surface chemistry of nano silver particles. Polyhedron. 2009;28:2522–30.

    Article  CAS  Google Scholar 

  • Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, et al. Twenty eight day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague–Dawley Rats. Inhal Toxicol. 2008;20:575–83.

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Choi JE, Choi J, Chung KH, Park K, Yi J. Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol Vitro. 2009;23:1076–84.

    Article  CAS  Google Scholar 

  • Kroemer G, Zamzami N, Susin SA. Mitochondrial control of apoptosis. Immunol Today. 1997;18:44–51.

    Article  PubMed  CAS  Google Scholar 

  • Kumaraguruparan R, Subapriya R, Viswanathan P, Nagini S. Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast. Clin Chim Acta. 2002;325:165–70.

    Article  PubMed  CAS  Google Scholar 

  • Ly JD, Grubb DR, Lawen A. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis. 2003;8:115–28.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell DB, Santone KS, Acosta D. Evaluation of cytotoxicity in cultured cells by enzyme leakage. J Tissue Cult Meth. 1980;6:113–6.

    Article  CAS  Google Scholar 

  • Miura N, Shinohara Y. Cytotoxic effect and apoptosis induction by silver nanoparticles in HeLa cells. Biochem Biophys Res Commun. 2009;390:733–7.

    Article  PubMed  CAS  Google Scholar 

  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Article  PubMed  CAS  Google Scholar 

  • Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006;311:622–7.

    Article  PubMed  CAS  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K. Assay of lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:331–58.

    Article  Google Scholar 

  • Park S, Lee YK, Jung M, Kim KH, Chung N, Ahn EK, et al. Cellular toxicity of various inhalable metal nanoparticles on human alveolar epithelial cells. Inhal Toxicol. 2007;19 Suppl 1:59–65.

    Article  PubMed  CAS  Google Scholar 

  • Pichaud N, Pellerin J, Fournier M, Gauthier-Clerc S, Rioux P, Pelletier É. Oxidative stress and immunologic responses following a dietary exposure to PAHs in Mya arenaria. Chem Cent J. 2008;2:23.

    Article  PubMed  Google Scholar 

  • Samberg ME, Oldenburg SJ, Monteiro-Riviere NA. Evaluation of silver nanoparticle toxicity in skin in vivo and keratinocytes in vitro. Environ Health Perspect. 2010;118:407–13.

    Article  PubMed  CAS  Google Scholar 

  • Soto K, Garza KM, Murr LE. Cytotoxic effects of aggregated nanomaterials. Acta Biomater. 2007;3:351–8.

    Article  PubMed  CAS  Google Scholar 

  • Takenaka S, Karg E, Roth C, Schulz H, Ziesenis A, Heinzmann U, et al. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect. 2001;4:547–51.

    Google Scholar 

  • Tang J, Xiong L, Wang S, Wang J, Liu L, Li J, et al. Distribution, translocation and accumulation of silver nanoparticles in rats. J Nanosci Nanotechnol. 2009;9:4924–32.

    Article  PubMed  CAS  Google Scholar 

  • Vigneshwaran N, Kathe AA, Varadarajan PV, Nachane RP, Balasubramanya RH. Functional finishing of cotton fabrics using silver nanoparticles. J Nanosci Nanotechnol. 2007;7:1893–7.

    Article  PubMed  CAS  Google Scholar 

  • Xu T, Zhang N, Nichols HL, Shi DL, Wen XJ. Modification of nanostructured materials for biomedical applications. Mater Sci Eng C. 2007;27:579–94.

    Article  CAS  Google Scholar 

  • Xu XY, Yang QB, Bai J, Lu TC, Li YX, Jing XB. Fabrication of biodegradable electrospun poly(L-lactide-co-glycolide) fibers with antimicrobial nanosilver particles. J Nanosci Nanotechnol. 2008;8:5066–70.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (20090061120093), China Postdoctoral Science Foundation (20100481064), SRFDP (20090061120093), Research Foundation of Jilin University (200903115), and S&T Development Project Foundation of Jilin Province (201101057).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Juan Li or Yan-fei Qi.

Additional information

Xiu-ling Song and Bo Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, Xl., Li, B., Xu, K. et al. Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702 cells. Cell Biol Toxicol 28, 225–237 (2012). https://doi.org/10.1007/s10565-012-9218-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-012-9218-x

Keywords

Navigation