Isaac Scientific Publishing

Journal of Advances in Nanomaterials

Selective Cytotoxicity of Counterion-Conjugated Charged Iron Oxide Nanoparticles: A Study with Lymphoblastoid Raji Cells

Download PDF (892.4 KB) PP. 45 - 56 Pub. Date: December 1, 2018

DOI: 10.22606/jan.2018.34001

Author(s)

  • Goutam Ghosh*
    UGC-DAE Consortium for Scientific Research, Mumbai Centre, Trombay, Mumbai 400085, India
  • Archana Mukherjee
    Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India
  • Hari Narayan Bhilwade
    Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, India;Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, India
  • Alka Gupta
    Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India
  • Aruna Korde
    Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India
  • Rita Mukhopadhyaya*
    Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India

Abstract

The cytotoxicity of counterions-conjugated charged iron oxide nanoparticles (IONPs) was studied with lymphoblastoid Raji cells and was compared with peripheral blood lymphocytes. IONPs were coated either with tri-potassium citrate (TKC), or with cetylpyridinium chloride (CPC). TKC coated IONPs were negatively charged and K+ counterions conjugated nanoparticles, and CPC coated IONPs were positively charged Cl- counterions conjugated nanoparticles. The cells were incubated with IONPs at 37 °C for 24 h and the cytotoxicity was studied by measuring the cell viability using MTT and LDH assays. The cytotoxicity of IONPs was further assessed through DNA fragmentation assay. Morphology of Raji cells was also observed by TEM. We have used a modified membrane lysis model to understand the cell death via cell membrane lysis due to counterions diffusion upon binding of IONPs.

Keywords

Charged nanoparticles, Raji cells, blood lymphocytes, cell viability, cell membrane lysis.

References

[1] G. Oberd?rster, “Safety assessment for nanotechnology and nanomedicine: Concepts of nanotoxicology”, Journal of Internal Medicine, vol. 267, pp. 89–105, 2010.

[2] C. E. Dreaden, A. M. Alkilany, X. Huang, C. J. Murphy, M. A. El-Sayed, “The golden age: gold nanoparticles for biomedicine”, Chemical Society Reviews, vol. 41, pp. 2740–2779, 2012.

[3] L. Dykman, N. Khlebtsov, “Gold nanoparticles in biomedical applications: recent advances and perspectives”, Chemical Society Reviews, vol. 41, pp. 2256–2282, 2012.

[4] F. Jia, X. Liu, L. Li, S. Mallapragada, B. Narasimhan, Q. Wang, “Multifunctional nanoparticles for targeted delivery of immune activating and cancer therapeutic agents”, Journal of Controlled Release, vol. 172, pp. 1020–1034, 2013.

[5] L. Mahmudin, E. Suharyadi, A. Bambang, S. Utomo, K. Abraha, “Optical properties of silver nanoparticles for surface plasmon resonance (SPR)-based biosensor applications”, Journal of Modern Physics, vol. 6, pp. 1071–1076, 2015.

[6] C. C. Berry, A. S. G. Curtis, “Functionalisation of magnetic nanoparticles for applications in biomedicine”, Journal of Physics D: Applied Physics, vol. 36, pp. R198–R206, 2003.

[7] Q. A. Pankhurst, J. Connolly, S. K. Jones, J. Dobson, “Applications of magnetic nanoparticles in biomedicine”, Journal of Physics D: Applied Physics, vol. 36, pp. R167–R181, 2003.

[8] S. Mornet, S. Vasseur, F. Grasset, E. Duguet, “Magnetic nanoparticle design for medical diagnosis and therapy”, Journal of Materials Chemistry, vol. 14, pp. 2161–2175, 2004.

[9] I. Safarik, M. Safarikova, “Magnetic techniques for the isolation and purification of proteins and peptides”, Biomagnetic Research and Technology, vol. 2, pp. 7(1–17), 2004.

[10] T. Neuberger, B. Schopf, H. Hofmann, M. Hofmann, B. von Rechenberg, “Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system”, Journal of Magnetism and Magnetic Materials, vol. 293, pp. 483–496, 2005.

[11] S. Laurent, D. Forge, M. Port, A. Roch, C. Robic, L. V. Elst, R. N. Muller, “Magnetic iron oxide nanoparticles: Synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications”, Chemical Reviews, vol. 108, pp. 2064–2110, 2008.

[12] K. C. Barick, M. Aslam, Y. P. Lin, D. Bahadur, P. V. Prasad, “Novel and efficient MR active aqueous colloidal Fe3O4 nanoassemblies”, Journal of Materials Chemistry, vol. 19, pp. 7023–7029, 2009.

[13] C. Fang, M. Zhang, “Multifunctional magnetic nanoparticles for medical imaging applications”, Journal of Materials Chemistry, vol. 19, pp. 6258–6266, 2009.

[14] S. H. Moghimi, A. C. Hunter, J. C. Murray, “Long-circulating and target-specific nanoparticles: Theory to practice”, Pharmacological Reviews, vol. 53, pp. 283–318, 2001.

[15] J. W. M. Bulte, D. L. Kraitchman, “Iron oxide MR contrast agents for molecular and cellular imaging”, NMR Biomedicine, vol 17, pp. 484–499, 2004.

[16] B. S. Zolnik, A. Gonzalez-Fernandez, N. Sadrieh, M. A. Dobrovolskaia, “Minireview: Nanoparticles and the immune system”, Endocrinology, vol. 151, pp. 458–465, 2010.

[17] H. Shi, R. Magaye, V. Castranova, J. Zhao, “Titanium dioxide nanoparticles: A review of current toxicological data”, Part Fibre Toxicology, vol. 10, pp. 15(1-33), 2013.

[18] F. Dilnawaz, A. Singh, C. Mohanty, S. K. Sahoo, “Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy”, Biomaterials, vol. 31, pp. 3694–3706, 2010.

[19] L. Wang, H. Zhang, B. Chen, G. Xia, S. Wang, J. Cheng, Z. Shao, C. Gao, W. Bao, L. Tian, Y. Ren, P. Xu, X. Cai, R. Liu, X. Wang, “Effect of magnetic nanoparticles on apoptosis and cell cycle, induced by wogonin in Raji cells”, International Journal of Nanomedicine, vol. 7, vol. 789–798, 2012.

[20] S. Naqvi, M. Samim, M. Abdin, F. J. Ahmed, A. Maitra, C. Prashant, A. K. Dinda, “Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress”, International Journal of Nanomedicine, vol. 5, pp. 983–989, 2010.

[21] E. Pawelczyk, A. S. Arbab, A. Chaudhry, A. Balakumaran, P. G. Robey, J. A. Frank, “In vitro model of bromodeoxyuridine or iron oxide nanoparticle uptake by activated macrophages from labeled stem cells: implications for cellular therapy”, Stem cells, vol. 26, pp. 1366–1375, 2008.

[22] Y. Ge, Y. Zhang, S. He, F. Nie, G. Teng, N. Gu, “Fluorescence modified chitosan-coated magnetic nanoparticles for high-efficient cellular imaging”, Nanoscale Research Letter, vol. 4, pp. 287–295, 2009.

[23] G. J. Delcroix, M. Jacquart, L. Lemaire, L. Sindji, F. Franconi, J. J. Le Jeune, C. N. Montero-Menei, “Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: In vitro characterization and migration potential in rat brain”, Brain Research, vol. 1255, pp. 18–31, 2009.

[24] G. Liu, J. Gao, H. Ai, X. Chen, “Applications and potential toxicity of magnetic iron oxide nanoparticles”, Small, vol. 9, pp. 1533–1545, 2013.

[25] N. B. La Thangue, D. J. Kerr, “Predictive biomarkers: a paradigm shift towards personalized cancer medicine”, Nature Reviews Clinical Oncology, vol. 8, pp. 587–596, 2011.

[26] C. O. Madu, Y. Lu, “Novel diagnostic biomarkers for prostate cancer”, Journal of Cancer, vol. 1, pp. 150–177, 2010.

[27] D. C. Gadsby, “Ion channels versus ion pumps: the principal difference, in principle”, Nature Reviews Molecular Cell Biology, vol. 10, pp. 344–352, 2009.

[28] J. Chen, T. Liu, T. Gao, L. Gao, L. Zhou, M. Cai, Y. Shi, W. Xiong, J. Jiang, T. Tong, H. Wang, “Variation in carbohydrates between cancer and normal cell membranes revealed by super‐resolution fluorescence imaging”, Advanced Science, vol. 3, pp. 1600270(1–9), 2016.

[29] L. Ghitescu, A. Fixman, “Surface-charge distribution on the endothelial-cell of liver sinusoids”, Journal of Cell Biology, vol. 99, pp. 639–647, 1984.

[30] A. L. Baldwin, N. Z. Wu, D. L. Stein, “Endothelial surface-charge of intestinal mucosal capillaries and its modulation by dextran”, Microvascular Research, vol. 42, pp. 160–178, 1991.

[31] A. C. Fleischer, C. K. Payne, “Nanoparticle-cell interactions: molecular structure of the protein corona and cellular outcomes”, Accounts of Chemical Research, vol. 47, pp. 2651?2659, 2014.

[32] E. C. Cho, J. W. Xie, P. A. Wurm, Y. N. Xia, “Understanding the role of surface charges in cellular adsorption versus internalization by selectively removing gold nanoparticles on the cell surface with a I2/KI etchant”, Nano Letter, vol. 9, pp. 1080–1084, 2009.

[33] S. A. Shah, A. Majeed, M. A. Shafique, K. Rashid, A. U. Awan, “Cell viability study of thermo-responsive core-shell superparamagnetic nanoparticles for multimodal cancer therapy”, Applied Nanoscience, vol. 4, pp. 227–232, 2014.

[34] G. Ghosh, L. Panicker, R. S. Ningthoujam, K. C. Barick, R. Tewari, “Counterion induced irreversible denaturation of hen egg white lysozyme upon electrostatic interaction with iron oxide nanoparticles: A predicted model”, Colloids and Surfaces B: Biointerfaces, vol. 103, pp. 267–274, 2013.

[35] G. Ghosh, “Counterion effects in protein nanoparticle electrostatic binding: a theoretical study”, Colloids and Surfaces B: Biointerfaces, vol. 128, pp. 23–27, 2015.

[36] G. Ghosh, L. Panicker, K. C. Barick, “Selective binding of proteins on functional nanoparticles via reverse charge parity model: an in vitro study”, Materials Research Express, vol. 1, pp. 015017(1–12), 2014.

[37] G. Ghosh, L. Panicker, “Interaction of human hemoglobin with charged ligand-functionalized iron oxide nanoparticles and effect of counterions”, Journal of Nanoparticle Research, vol. 16, pp. 2800(1–10), 2014.

[38] G. Ghosh, L. Panicker, K. C. Barick, “Protein nanoparticle electrostatic interaction: Size dependent counterions induced conformational change of hen egg white lysozyme”, Colloids Surfaces B: Biointerfaces, vol. 118, pp. 1–6, 2014.

[39] J. C. Stockert, A. Blázquez-Castro, M. Ca?ete, R. W. Horobin, A. Lillanueva, “MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets”, Acta Histochemica, vol. 114, pp. 785–796, 2012.

[40] F. K. M. Chan, K. Moriwaki, M. J. De Rosa, “Detection of necrosis by release of lactate dehydrogenase (LDH) activity”, Methods in Molecular Biology, vol. 979, pp. 65–70, 2013.

[41] H. N. Bhilwade, S. Jayakumar, R. C. Chaubey, “Age-dependent changes in spontaneous frequency of micronucleated erythrocytes in bone marrow and DNA damage in peripheral blood of Swiss mice”, Mutation Research, vol. 770, pp. 80–84, 2014.

[42] A. M. Schrand, J. J. Schlager, L. Dai, S. M. Hussain, “Preparation of cells for assessing ultrastructural localization of nanoparticles with transmission electron microscopy”, Nature Protocol, vol. 5, pp. 744–757, 2010.

[43] A. Chen, W. Le, Y. Wang, Z. Li, D. Wang, L. Ren, L. Lin, S. Cui, J. J. Hu, Y. Hu, P. Yang, R. C. Ewing, D. Shi, Z. Cui, “Targeting negative surface charges of cancer cells by multifunctional nanoprobes”, Theranotics, vol. 6, pp. 1887–1898, 2016.

[44] G. Kroemer, W. S. El-Deiry, P. Golstein, M. E. Peter, D. Vaux, P. Vandenabeele, B. Zhivotovsky, M. V. Blagosklonny, W. Malorni, R. A. Knight, M. Piacentini, S. Nagata, G. Melino, “Classification of cell death: recommendations of the nomenclature committee on cell death”, Cell Death & Differentiation, vol. 12, pp. 1463–1467, 2005.

[45] P. Golstein, G. Kroemer, “Cell death by necrosis: towards a molecular definition”, Trends in Biochemical Sciences, vol. 32, pp. 37–43, 2006.

[46] W. Martinet, D. M. Schrijvers, G. R. de Mayer, “Necrotic cell death in atherosclerosis”, Basic Research in Cardiology, vol. 106, pp. 749–760, 2011.

[47] J. C. Shillcock, D. H. Boal, “Entropy-driven instability and rupture of fluid membranes”, Biophysical Journal, vol. 71, pp. 317–326, 1996.

[48] J. Wolfe, (2015) “Cellular thermodynamics: the molecular and macroscopic view” in eLS, Wiley, 2015, pp. 1–13.

[49] A. A. Marino, D. M. Morris, M. A. Schwalke, I. G. Iliev, S. Rogers, “Electrical potential measurements in human breast cancer and benign lesions”, Tumour Biology, vol. 15, pp. 147–152, 1994.

[50] C. N. Cutter, W. J. Dorsa, A. Handie, S. Rodriguez-Morales, X. Zhou, P. J. Breen, C. M. Compadre, “Antimicrobial activity of cetylpyridinium chloride washes against pathogenic bacteria on beef surfaces”, Journal of Food Protection, vol. 63, pp. 593–600, 2000.

[51] S. Zhang, H. Gao, G. Bao, “Physical principles of nanoparticle cellular endocytosis”, ACS Nano, vol. 9, pp. 8655–8671, 2015.

[52] X. Meng, N. H. Riordan, H. D. Riordan, N. Mikirova, J. Jackson, M. J. Gonzalez, J. R. Miranda-Massari, E. Mora, W. Trinidad Castillo, “Cell membrane fatty acid composition differs between normal and malignant cell lines”, Puerto Rico Health Sciences Journal, vol. 23, pp. 103–106, 2004.

[53] H. J. Cohen, “Human lymphocyte surface immunoglobulin capping. Normal characteristics and anomalous behavior of chronic lymphocytic leukemia lymphocytes”, The Journal of Clinical Investigation, vol. 55, pp. 84–93, 1975.

[54] U. Cavallaro, G. Christofori, “Cell adhesion and signalling by cadherins and Ig-CAMs in cancer”, Nature Reviews Cancer, vol. 4, pp. 118–132, 2004.