Skip to main content
Log in

Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Cellular uptake, cytotoxicity, and mechanisms of cytotoxicity of the positively charged Au nanoparticles (NPs) were examined in A549 cells, which are one of the most characterized pulmonary cellular systems. Positively charged Au NPs were prepared by chemical reduction using chitosan. The dimension and surface charge of Au NPs were examined by transmission electron microscopy (TEM), dynamic light scattering, and zeta potential measurements. The uptake of Au NPs into A549 cells was also monitored using TEM and dark-field microscopy (DFM) and z-stack confocal microRaman spectroscopy. DFM live cell imaging was also performed to monitor the entry of chitosan Au NPs in real time. The cytotoxic assay, using both methylthiazol tetrazolium and lactate dehydrogenase assays revealed that positively charged Au NPs decreased cell viability. Flow cytometry, DNA fragmentation, real-time PCR, and western blot analysis suggest that positively charged chitosan Au NPs provoke cell damage through both apoptotic and necrotic pathways.

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.

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

Similar content being viewed by others

References

  • Ahamed M, Akhtar MJ, Siddiqui MA, Ahmad J, Musarrat J, Al-Khedhairy AA, AlSalhi MS, Alrokayan SA (2011) Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells. Toxicology 283:101–108

    Article  CAS  Google Scholar 

  • Akhtar MJ, Ahamed M, Kumar S, Siddiqui H, Patil G, Ashquin M, Ahmad I (2010) Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells. Toxicology 276:95–102

    Article  CAS  Google Scholar 

  • Arora S, Jain J, Rajwade JM, Paknikar KM (2008) Cellular responses induced by silver nanoparticles: in vitro studies. Toxicol Lett 179:93–100

    Article  CAS  Google Scholar 

  • Arvizo RR, Miranda OR, Thompson MA, Pabelick CM, Bhattacharya R, Robertson JD, Rotello VM, Prakash YS, Mukherjee P (2010) Effect of nanoparticle surface charge at the plasma membrane and beyond. Nano Lett 10:2543–2548

    Article  CAS  Google Scholar 

  • Auffan M, Rose J, Bottero JY, Lowry GV, Jolivet JP, Wiesner MR (2009) Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. Nat Nanotechnol 4:634–641

    Article  CAS  Google Scholar 

  • 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 

  • Choi SY, Jeong S, Jang SH, Park J, Park JH, Ock KS, Lee SY, Joo SW (2012) In vitro toxicity of serum protein-adsorbed citrate-reduced gold nanoparticles in human lung adenocarcinoma cells. Toxicol In Vitro 26:229–237

    Article  CAS  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 

  • Duceppe N, Tabrizian M (2010) Advances in using chitosan-based nanoparticles for in vitro and in vivo drug and gene delivery. Expert Opin Drug Deliv 7:1191–1207

    Article  CAS  Google Scholar 

  • Founce TA, White J, Matthaei KI (2008) Integrated research into nanoparticle-protein corona: a new focus for safe, sustainable and equitable development. Nanomedicine 3:859–866

    Article  Google Scholar 

  • Goodman CM, McCusker CD, Yilmaz T, Rotello VM (2004) Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem 15:897–900

    Article  CAS  Google Scholar 

  • Gratton SEA, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, DeSimone JM (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105:11613–11618

    Article  CAS  Google Scholar 

  • Haynes CL (2010) The emerging field of nanotoxicology. Anal Bioanal Chem 398:587–588

    Article  CAS  Google Scholar 

  • Hu W, Peng C, Lv M, Li X, Zhang Y, Chen N, Fan C, Huang Q (2011a) Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano 5(5):3693–3700

    Article  CAS  Google Scholar 

  • Hu XY, Fang Q, Wang JS, Xie JQ, Chai BS, Li FQ, Cui X, Yang Y (2011b) Over-expression of aldehyde dehydrogenase-2 protects against H2O2-induced oxidative damage and apoptosis in peripheral blood mononuclear cells. Acta Pharmacol Sin 32(2):245–252

    Article  CAS  Google Scholar 

  • Jeong S, Choi SY, Park J, Seo JH, Park J, Cho KC, Joo SW, Lee SY (2011) Low-toxicity chitosan gold nanoparticles for small hairpin RNA delivery in human lung adenocarcinoma cells. J Mater Chem 21(36):13853–13859

    Article  CAS  Google Scholar 

  • Kang B, Mackey MA, El-Sayed MA (2010) Nuclear targeting of gold nanoparticles in cancer cells induces DNA damage, causing cytokinesis arrest and apoptosis. J Am Chem Soc 132:1517–1519

    Article  CAS  Google Scholar 

  • Khan JA, Pillai B, Das TK, Singh Y, Maiti S (2007) Molecular effects of uptake of gold nanoparticles in HeLa cells. ChemBioChem 8:1237–1240

    Article  CAS  Google Scholar 

  • Lin J, Zhang H, Chen Z, Zheng Y (2010) Penetration of lipid membranes by gold nanoparticles: insights into cellular uptake, cytotoxicity, and their relationship. ACS Nano 4(9):5421–5429

    Article  CAS  Google Scholar 

  • Liu S, Xu L, Zhang T, Ren G, Yang Z (2010) Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology 267:172–177

    Article  CAS  Google Scholar 

  • Lynch I, Salvati A, Dawson KA (2009) What does the cell see? Nat Nanotechnol 4:546–547

    Article  CAS  Google Scholar 

  • Mitchell DB, Santone KS, Acosta D (1980) Evaluation of cytotoxicity in cultured cells by enzyme leakage. J Tissue Cult Methods 6:113–116

    Article  CAS  Google Scholar 

  • Nel A, Xia T, Mädler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627

    Article  CAS  Google Scholar 

  • Pan Y, Leifert A, Ruau D, Neuss S, Bornemann J, Schmid G, Brandau W, Simon U, Jahnen-Dechent W (2009) Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small 5(18):2067–2076

    Article  CAS  Google Scholar 

  • Patra HK, Banerjee S, Chaudhuri U, Lahiri P, Dasgupta AKr (2007) Cell selective response to gold nanoparticles. Nanomedicine 3:111–119

    Article  CAS  Google Scholar 

  • Pernodet N, Fang X, Sun Y, Bakhtina A, Ramakrishnan A, Sokolov J, Ulman A, Rafailovich M (2006) Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. Small 2:766–773

    Article  CAS  Google Scholar 

  • Perumal OP, Inapagolla R, Kannan S, Kannan SM (2008) The effect of surface functionality on cellular trafficking of dendrimers. Biomaterials 29:3469–3476

    Article  CAS  Google Scholar 

  • Schaeublin NM, Braydich-Stolle L, Schrand AM, Miller JM, Hutchison J, Schlager JJ, Hussain SM (2011) Surface charge of gold nanoparticles mediates mechanism of toxicity. Nanoscale 3:410–420

    Article  CAS  Google Scholar 

  • Simpson CA, Huffman BJ, Gerdon AE, Cliffel DE (2010) Unexpected toxicity of monolayer protected gold clusters eliminated by PEG-thiol place exchange reactions. Chem Res Toxicol 23:1608–1616

    Article  CAS  Google Scholar 

  • Uboldi C, Bonacchi D, Lorenzi G, Hermanns MI, Pohl C, Baldi G, Unger RE, Kirkpatrick CJ (2009) Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441. Part Fibre Toxicol 6:18–29

    Article  Google Scholar 

  • Unfried K, Albrecht C, Klotz LO, Mikecz AV, Beck SG, Schins RPF (2007) Cellular responses to nanoparticles: target structures and mechanisms. Nanotoxicology 1:52–71

    Article  CAS  Google Scholar 

  • Wei D, Qian W (2008) Facile synthesis of Ag and Au nanoparticles utilizing chitosan as a mediator agent. Colloid Surf B 62:136–142

    Article  CAS  Google Scholar 

  • Yen HJ, Hsu SH, Tsai CL (2009) Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small 5:1553–1561

    Article  CAS  Google Scholar 

  • Zhang Y, Yang M, Portney NG, Cui D, Budak G, Ozbay E, Ozkan M, Ozkan CS (2008) Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells. Biomed Microdevices 10:321–328

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We acknowledge the financial support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012-0000906, 2011-0027696, 2011-0014514) and the Development of Characterization Techniques for Nano-materials Safety Project of KRCF. This subject is supported by Korea Ministry of Environment as “Environmental Health R&D Program”.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Sang-Woo Joo or So Yeong Lee.

Additional information

Seon Young Choi and Soo Hwa Jang contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, S.Y., Jang, S.H., Park, J. et al. Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells. J Nanopart Res 14, 1234 (2012). https://doi.org/10.1007/s11051-012-1234-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-012-1234-5

Keywords

Navigation