Short-term effects of ultrahigh concentration cationic silica nanoparticles on cell internalization, cytotoxicity, and cell integrity with human breast cancer cell line (MCF-7)

  • Ji Hyun Seog
  • Bokyung Kong
  • Dongheun Kim
  • Lauren M. Graham
  • Joon Sig Choi
  • Sang Bok Lee
Research Paper


High concentrations of cationic colloidal silica nanoparticles (CCS-NPs) have been widely used for the enrichment of plasma membrane proteins. However, the interaction between the CCS-NPs and cells under the required concentration for the isolation of plasma membrane are rarely investigated. We evaluated the internalization and toxicity of the 15 nm CCS-NPs which were exposed at high concentrations with short time in human breast cancer cells (MCF-7) with transmission electron microscopy, energy dispersive X-ray spectroscopy, inductively coupled plasma atomic emission spectroscopy, and colorimetric assays. The NPs were observed throughout the cells, particularly in the cytoplasm and the nucleus, after short incubation periods. Additionally, the NPs significantly influenced the membrane integrity of the MCF-7 cells.


Cationic colloidal silica nanoparticle Plasma membrane enrichment Human breast cancer cells (MCF-7) Toxicity Proteomics Fast uptake Health effects 

Supplementary material

11051_2014_2823_MOESM1_ESM.docx (1.4 mb)
Supplementary material 1 (DOCX 1408 kb)


  1. Aillon KL, Xie Y, El-Gendy N, Berkland CJ, Forrest ML (2009) Effects of nanomaterial physicochemical properties on in vivo toxicity. Adv Drug Deliv Rev 61:457–466CrossRefGoogle Scholar
  2. Alkilany AM, Murphy CJ (2010) Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? J Nanopart Res 12:2313–2333CrossRefGoogle Scholar
  3. Arvizo RR, Miranad 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 10:2543–2548CrossRefGoogle Scholar
  4. Bouwmeester H, Dekkers S, Noordam MY, Hagens WI, Bulder AS, de Heer C, ten Voorde SE, Wijnhoven SW, Marvin HJ, Sips AJ (2009) Review of health safety aspects of nanotechnologies in food production. Regul Toxicol Pharmacol 53:52–56CrossRefGoogle Scholar
  5. Chaney LK, Jacobson BS (1983) Coating cells with colloidal silica for high yield isolation of plasma membrane sheets and identification of transmembrane proteins. J Biol Chem 258:10062–10072Google Scholar
  6. Chang JS, Chang KL, Hwang DF, Kong ZL (2007) In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol 41:2064–2068CrossRefGoogle Scholar
  7. Durr E, Yu J, Krasinska KM, Carver LA, Yates JR, Testa JE, Oh P, Schnitzer JE (2004) Direct proteomic mapping of the lung microvascular endothelial cell surface in vivo and in cell culture. Nat Biotechnol 22:985–992CrossRefGoogle Scholar
  8. Halas NJ (2008) Nanoscience under glass: the versatile chemistry of silica nanostructures. ACS Nano 2:179–183CrossRefGoogle Scholar
  9. Kim YJ, Yu MR, Park HO, Yang SI (2010) Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by silica nanomaterials in human neuronal cell line. Mol Cell Toxicol 6:337–344Google Scholar
  10. Kong B, Seog JH, Graham LM, Lee SB (2011) Experimental considerations on the cytotoxicity of nanoparticles. Nanomedicine 6:929–941CrossRefGoogle Scholar
  11. Kovalenko GA, Shitova NB, Sokolovskii VD (1981) Immobilization of oxyreductases on inorganic supports based on alumina. Immobilization of lactate dehydrogenase on alumina by adsorption. Biotechnol Bioeng 23:1721–1734CrossRefGoogle Scholar
  12. Kuhlbusch TAJ, Asbach C, Fissan H, Goehler D, Stintz M (2011) Nanoparticle exposure at nanotechnology workplaces: a review. Part Fibre Toxicol 8:22CrossRefGoogle Scholar
  13. Kumar P, Pirjola L, Ketzel M, Harrison RM (2013) Nanoparticle emissions from 11 non-vehicle exhaust sources—a review. Atmos Environ 67:252–277CrossRefGoogle Scholar
  14. Lee H, Larson RG (2009) Multiscale modeling of dendrimers and their interactions with bilayers and polyelectrolytes. Molecules 14:423–438CrossRefGoogle Scholar
  15. Leroueil PR, Berry SA, Duthie K, Han G, Rotello VM, McNerny DQ, Baker JR, Orr BG, Holl MM (2008) Wide varieties of cationic nanoparticles induce defects in supported lipid bilayers. Nano Lett 8:420–424CrossRefGoogle Scholar
  16. Lin J, Alexander-Katz A (2013) Cell membranes open “doors” for cationic nanoparticles/biomolecules: insights into uptake kinetics. ACS Nano 7:10799–10808CrossRefGoogle Scholar
  17. Lu J, Liong M, Li Z, Zink JI, Tamanoi F (2010) Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 6:1794–1805CrossRefGoogle Scholar
  18. Madani F, Lindberg S, Langel U, Futaki S, Gräslund A (2011) Mechanisms of cellular uptake of cell-penetrating peptides. J Biophys 2011:414729CrossRefGoogle Scholar
  19. Mathias RA, Chen YS, Goode RJ, Kapp EA, Mathivanan S, Moritz RL, Zhu HJ, Simpson RJ (2011) Tandem application of cationic colloidal silica and Triton X-114 for plasma membrane protein isolation and purification: towards developing an MDCK protein database. Proteomics 11:1238–1253CrossRefGoogle Scholar
  20. Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–627CrossRefGoogle Scholar
  21. Niemeyer CM (2001) Nanoparticles, proteins, and nucleic acids: biotechnology meets materials science. Angew Chem Int Ed 40:4128–4158CrossRefGoogle Scholar
  22. Qhobosheane M, Santra S, Zhang P, Tan W (2001) Biochemically functionalized silica nanoparticles. Analyst 126:1274–1278CrossRefGoogle Scholar
  23. Rahbar AM, Fenselau C (2004) Integration of Jacobson’s Pellicle Method into proteomic strategies for plasma membrane proteins. J Proteome Res 3:1267–1277CrossRefGoogle Scholar
  24. Ranjan S, Dasgupta N, Chakraborty AR, Samuel SM, Ramalingam C, Shanker R, Kumar A (2014) Nanoscience and nanotechnologies in food industries: opportunities and research trends. J Nanopart Res 16:2464CrossRefGoogle Scholar
  25. Robinson JM, Ackerman WET, Tewari AK, Kniss DA, Vandre DD (2009) Isolation of highly enriched apical plasma membranes of the placental syncytiotrophoblast. Anal Biochem 387:87–94CrossRefGoogle Scholar
  26. Shinkai M (2002) Functional magnetic particles for medical application. J Biosci Bioeng 94:606–613CrossRefGoogle Scholar
  27. Sozer N, Kokini JL (2009) Nanotechnology and its applications in the food sector. Trends Biotechnol 27:82–89CrossRefGoogle Scholar
  28. Stepnik M, Arkusz J, Smok-Pieniążek A, Bratek-Skicki A, Salvati A, Lynch I, Dawso KA, Gromadzińska J, De Jong WH, Rydzynski K (2012) Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles. Toxicol Appl Pharmacol 263:89–101CrossRefGoogle Scholar
  29. Wang L, Zhao W, Tan W (2008) Bioconjugated silica nano particles: development and applications. Nano Res 1:99–115CrossRefGoogle Scholar
  30. Wang J, Asbach C, Fissan H, Hulser T, Kaminski H, Kuhlbusch TAJ, Pui DYH (2012) Emission measurement and safety assessment for the production process of silicon nanoparticles in a pilotscale facility. J Nanopart Res 14:759–767CrossRefGoogle Scholar
  31. Yoon D, Woo D, Kim JH, Kim MK, Kim T, Hwang ES, Baik S (2011) Agglomeration, sedimentation, and cellular toxicity of alumina nanoparticles in cell culture medium. J Nanopart Res 13:2543–2551CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Ji Hyun Seog
    • 1
  • Bokyung Kong
    • 2
  • Dongheun Kim
    • 1
  • Lauren M. Graham
    • 3
  • Joon Sig Choi
    • 4
  • Sang Bok Lee
    • 1
    • 3
  1. 1.Graduate School of Nanoscience and TechnologyKorea Advanced Institute of Science and TechnologyDaejeonKorea
  2. 2.Corning Precision MaterialsAsanKorea
  3. 3.Department of Chemistry and BiochemistryUniversity of MarylandCollege ParkUSA
  4. 4.Department of BiochemistryChungnam National UniversityDaejeonKorea

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