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Toxicity Studies of Fullerenes and Derivatives

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Bio-Applications of Nanoparticles

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 620))

Abstract

Due to their unique properties, fullerenes, a model of carbon-based nanoparticles, have attracted considerable interest in many fields of research including material science and biomedical applications. The potential and the growing use of fullerenes and their mass production have raised several questions about their safety and environmental impact. Available data clearly shows that pristine C60 has no acute or sub-acute toxicity in a large variety of living organisms, from bacteria and fungal to human leukocytes, and also in drosophila, mice, rats and guinea pigs. In contrast to chemically—either covalently or noncovalently—modified fullerenes, some C60 derivatives can be highly toxic. Furthermore, under light exposure, C60 is an efficient singlet oxygen sensitizer. Therefore, if pristine C60 is absolutely nontoxic under dark conditions, this is not the case under UV-Visible irradiation and in the presence of O2 where fullerene solutions can be highly toxic through 1 O2 formation.

This chapter offers a general review of the studies on the toxicity of [60] fullerence or C60, the most abundant fullerene, and its derivatives.

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References

  1. Kroto HW, Heath JR, O’Brien SC et al. C60: Buckminsterfullerence. Nature 1985; 318:162–163.

    Article  CAS  Google Scholar 

  2. Smalley RE, Yakobson BI. The future of the fullerenes. Solid State Communications 1998; 107(11):597–606.

    Article  CAS  Google Scholar 

  3. Granja F, Dorantes-Dávila J, Morán-López IL et al. Electronic structure of some semiconductor fullerenes. Nanostructured Materials 1993; 3(1–6):469–477.

    Google Scholar 

  4. Spence JCH. The future of atomic resolution electron microscopy for materials science. Materials Science and Engineering Reports 1999; 26(1–2):1–49.

    Article  Google Scholar 

  5. Kuzmany H, Winter J, Burger B. Polymeric fullerenes. Synthetic Metals 1997; 85(1–3):1173–1177.

    Article  CAS  Google Scholar 

  6. Jensen AW, Wilson SR, Schuster DI. Biological applications of fullerenes. Bioorg Med Chem 1996; 4(6):767–79.

    Article  PubMed  CAS  Google Scholar 

  7. Wilson LJ, Cagle DW, Thrash TP et al. Metallofullerene drug design. Coordination Chemistry Reviews 1999; 190–192:199–207.

    Article  Google Scholar 

  8. Tsao N, Kanakamma P, Luh TY et al. Inhibition of escherichia coli-induced meningites by carboxyfullerene. Antimicrobial Agents and Chemotherapy 1999; 43(9):2273–7.

    PubMed  CAS  Google Scholar 

  9. Krusic PJ, Waserman E, Keizer PN et al. Radical reaction of C60. Science 1991; 254:1183–5.

    Article  PubMed  CAS  Google Scholar 

  10. Hirsh A. The chemistry of fullerenes: George Thieme Verlang. 1st ed. NY: 1994.

    Google Scholar 

  11. Yamakoshi YN, Yagami T, Fukuhara K et al. Solubilization of fullerenes into water with polyvinylpyrrolidone applicable to biological tests. J Chem Soc Chem Commun 1994; 4:517–18.

    Article  Google Scholar 

  12. Diederich F, Thilgen C. Covalent fullerene chemistry. Science 1996; 271(5247):317–323.

    Article  CAS  Google Scholar 

  13. Dugan LL, Gabrielsen JK, Yu SP. Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiology of Disease 1996; 3:129–35.

    Article  PubMed  CAS  Google Scholar 

  14. Dugan LL, Lovett EG, Quick J et al. Fullerene based antioxidants and neurodegenerative disorders. Parkinsonism and Related Disorders 2001; 7:243–46.

    Article  PubMed  Google Scholar 

  15. Dugan LL, Turetsky DM, Du C et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci USA 1997; 94:9434–9.

    Article  PubMed  CAS  Google Scholar 

  16. Gharbi N, Pressac M, Hadchouel M et al. [60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett 2005; 5(12):2578–85.

    Article  PubMed  CAS  Google Scholar 

  17. Arbogast J, Darmanyan A, Foote C et al. Photophysical properties of C60. J Phys Chem 1991; 95(1):11–12.

    Article  CAS  Google Scholar 

  18. Sera N, Tokiwa H, Miyata N. Mutagenicity of the fullerence C60-generated singlet oxygen dependent formation of lipid peroxides. Carcinogenosis 1996; 17(10):2163–9.

    Article  CAS  Google Scholar 

  19. Yamago S, Tokuyama H, Nakamura E et al. In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol 1995; 2:385–9.

    Article  PubMed  CAS  Google Scholar 

  20. Boutorine AS, Tokuyama H, Takasugi M et al. Fullerene-oligonucleotide conjugates: Photoinduced sequence-specific DNA cleavage. Angew Chem Int ed Engl 1994; 33(23–24):2462–5.

    Google Scholar 

  21. Nelson MA, Domann F, Bowden GT et al. Acute and subchronic exposure of topically applied fullerene extracts on the mouse skin. Toxicol Ind Health 1993; 9:623–30.

    PubMed  CAS  Google Scholar 

  22. Scrivens WA, Tour JM, Kreek KE et al. Synthesis of 14C labeled C60, its suspension in water, and its uptake by human keratinocytes. J Am Chem Soc 1994; 116:4517–8.

    Article  CAS  Google Scholar 

  23. Zakharenko LP, Zakharov IK, Lunegov SN et al. Somatic mosaicism demonstrates that fullerene C60 has no genetic toxicity. Biological Sciences 1994; 335:153–154.

    Google Scholar 

  24. Moussa F, Chrétien P, Dubois P et al. The influence of C60 powders on cultured human leukocytes. Fullerene Science and Technology 1995; 3:333–42.

    CAS  Google Scholar 

  25. Baierl T, Seidel A. In vitro effects of fullerenes C60 and fullerenes black on immunofunctions of macrophages. Fullerenes Science and Technology 1996; 5:1073.

    Google Scholar 

  26. Moussa F, Trivin F, Céolin R et al. Early effects of C60 administration in Swiss Mice: A preliminary account for in vivo C60 toxicity”. Fullerenes Science and Technology 1996; 4:21–29.

    CAS  Google Scholar 

  27. Moussa F, Pressac M, Hadchouel M et al. C60 fullerene toxicity: Preliminary account of an in vivo study. In: Pennington NJ, Kadish K, Ruoff R, eds. Fullerenes. Proceedings Series of the 19 1st Meeting of the Electrochem Soc 1997; 97–42:332–336.

    Google Scholar 

  28. Geerts A, De Bleser P, Hautekecte M et al. In: Arias IM, Boyer JL, Fausto N, Jakoby WB, Schater DA, Shafritz DA, eds. The Liver: Biology and Pathobiology. 3rd ed. New York: Raven Press Ltd., 1994:819–839.

    Google Scholar 

  29. Poli G. Pathogenesis of liver fibrosis: Role of oxidative stress. Mol Aspects Med 2000; 21:49–98.

    Article  PubMed  CAS  Google Scholar 

  30. Slater TF. Necrogenic action of carbon tetrachloride in the rat: A speculative mechanism based on activation. Nature 1966; 209:36–40.

    Article  PubMed  CAS  Google Scholar 

  31. Slater TF, Cheesman KH, Ingold KU et al. Carbon tetrachloride toxicity as a model for studying free-radical mediated liver injury. Trans R Soc London 1985; B311:633–645.

    Article  Google Scholar 

  32. Zakharenko LP, Zakharov IK, Vasiunina EA et al. Determination of the genotoxicity of fullerene C60 and fullerol using the method of somatic mosaics on cells of Drosophila melanogaster wing and SOS-chromotest. Genetika 1997; 33(3):405–9.

    PubMed  CAS  Google Scholar 

  33. Wainwright M, Falih AM. Fungal growth on buckminsterfullerene. Microbiology 1997; 143:2097–2098.

    Article  CAS  Google Scholar 

  34. Moussa F, Chrétien P, Pressac M et al. Preliminary study of the influence of cubic C60 on cultured human monocytes: Lack of interleukin-1β secretion. Fullerenes Science and Technology 1997; 5:503–510.

    CAS  Google Scholar 

  35. Moussa F, Roux S, Pressac M et al. In vivo reaction between [60]fullerenes and vitamin A in mouse liver. N J Chem 1998; 32:989–92.

    Article  Google Scholar 

  36. Chiron JP, Lamande J, Moussa F et al. Effect of “micronized” C60 fullerene on the microbial growth in vitro. Ann Pharm Fr 2000; 58(3):170–5.

    PubMed  CAS  Google Scholar 

  37. Mori T, Takada H, Ito et al. Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis. Toxicology 2006; 225(1):48–54.

    Article  PubMed  CAS  Google Scholar 

  38. Ungurenasu C, Airinei A. Highly stable C60/poly(vinylpyrrolidone) charge-transfer complexes afford new predictions for biological applications of underivatized fullerenes. J Med Chem 2000; 43(16):3186–8.

    Article  PubMed  CAS  Google Scholar 

  39. Satoh M, Matsuo K, Kiriya H et al. Effects of acute and short term repeated application of fullerene C60 on agonist-induced responses in various tissues of Guinea pig and rats. Gen Pharmac 1995; 26(7):1533–8.

    CAS  Google Scholar 

  40. Tsuchiya T, Oguri I, Yamakoshi YN et al. Novel harmful effects of (60)fullerene on mouse embryos in vitro and in vivo. FEBS Lett 1996; 393:139–145.

    Article  PubMed  Google Scholar 

  41. Oberdorster E. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ Health Perspect 2004; 112(10):1058–62.

    PubMed  CAS  Google Scholar 

  42. Barnaby JF. New York Times, 2004.

    Google Scholar 

  43. Rittner MN. Confusion in the mass media. Nanoparticles News, 2004.

    Google Scholar 

  44. Sayes CM, Fortner JD, Guo W et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett 2004; 4(10):1881–7.

    Article  CAS  Google Scholar 

  45. Sayes CM, Gobin AM, Ausman KD et al. Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials 2005; 26(36):7587–95.

    Article  PubMed  CAS  Google Scholar 

  46. Isakovic A, Markovic Z, Todorovic-Markovic B et al. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol Sci 2006; 91(1):173–83.

    Article  PubMed  CAS  Google Scholar 

  47. Oberdorster E, Zhu S, Blickley M et al. Ecotoxicology of carbon-based engineered nanoparticles: Effects of fullerene (C60) on aquatic organisms. Carbon 2006; 44(6):1112–1120.

    Article  CAS  Google Scholar 

  48. Lovern SB, Klaper R. Daphnia magna mortality when exposed to titanium dioxide and fullerene (C60) nanoparticles. Environ Toxicol Chem 2006; 25(4):1132–7.

    Article  PubMed  CAS  Google Scholar 

  49. Rajagopalan P, Wudl F, Schinazi RF et al. Pharmacokinetics of a water-soluble fullerene in rats. Antimicrob Agents Chemother 1996; 40(10):2262–5.

    PubMed  CAS  Google Scholar 

  50. Schuster DI, Wilson SR, Schinagi RF. Anti-human immunodeficiency virus activity and cytotoxicity of derivatized buckministerfullerenes. Bioorg Med Chem Lett 1996; 6:1253–1256.

    Article  CAS  Google Scholar 

  51. Gharbi N, Pressac M, Tomberli V et al. In vivo behaviour of two C60 derivatives. Electrochemical Society Proceedings 2000; 240-43.

    Google Scholar 

  52. Dugan LL, Lovett EG, Quick KL et al. United States Patent Application Publication, 2003, (Pub no US 2003; 2003/0162837 A1, Pub. Date: Aug. 28).

    Google Scholar 

  53. Rancan F, Rosan S, Boehm F et al. Cytotoxicity and photocytotoxicity of a dendritic C(60) mono-adduct and a malonic acid C(60) tris-adduct on Jurkat cells. J Photochem Photobiol B 2002; 67:157–162.

    Article  PubMed  CAS  Google Scholar 

  54. Bosi S, Feruglio L, Da Ros T et al. Hemolytic effects of water-soluble fullerene derivatives. J Med Chem 2004; 47(27):6711–5.

    Article  PubMed  CAS  Google Scholar 

  55. Yang J, Wang Y, Rassat A et al. Synthesis of novel highly water-soluble 2∶1 cyclodextrin/fullerene conjugates involving the secondary rim of b-cyclodextrin. Tetrahedron 2004; (60):12163–8.

    Google Scholar 

  56. Yamawaki H, Iwai N. Cytotoxicity of water-soluble fullerene in vascular endothelial cells. Am J Physiol Cell Physiol 2006; 290(6):C1495–502.

    Article  PubMed  CAS  Google Scholar 

  57. Colvin V, Sayes CM, Ausman KD et al. Environmental chemistry and effects of engineered nanostructures [Abstract]. In: Anaheimn CA, ed. Proceedings of the 227th ACS National Meeting. IEC 18. Washington, DC: American Chemical Society, 2004, (Available: http://oasys2.confex.com/acs/227nm/techprogram/ P721792. HTM [accessed 20 May 2004]).

    Google Scholar 

  58. Brant JA, Labille J, Bottero JY et al. Characterizing the impact of preparation method on fullerene cluster structure and chemistry. Langmuir 2006; 22(8):3878–85.

    Article  PubMed  CAS  Google Scholar 

  59. Andrievsky G, Klochkov V, Derevyanchenko L. Is C60 fullerene molecule toxic?! Fullerenes Nanotubes and Carbon Nanostructures 2005; (13):1–14.

    Google Scholar 

  60. Avdeev MV, Khokhryakov AA, Tropin TV et al. Structural features of molecular-colloidal solutions of C60 fullerenes in water by small-angle neutron scattering. Langmuir 2004; 20(11):4363–8.

    Article  PubMed  CAS  Google Scholar 

  61. Zha QQ, Wei XW, Sun J et al. Synthesis and properties of [60]fullerene based nanocomposites. Proceedings of the 7th Biennial international Workshop on fullerenes and atomic clusters, St. Petersburg, Russia, June 27-July 1, 2005. Abingdon, UK: Taylor and Francis, 2006.

    Google Scholar 

  62. Isakovic A, Markovic Z, Nikolic N et al. Inactivation of nanocrystalline C60 cytotoxicity by gamma-irradiation. Biomaterials 2006; 27(29):5049–58.

    Article  PubMed  CAS  Google Scholar 

  63. Deguchi S, Mukai S, Tsudome M et al. Facile generation of fullerene nanoparticles by hand-grinding. Advanced Materials 2006; 18(6):733–737.

    Article  CAS  Google Scholar 

  64. Jia G, Wang H, Yan L et al. Cytotoxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol 2005; 39(5):1378–83.

    Article  PubMed  CAS  Google Scholar 

  65. Fiorito S, Serafino A, Andreola F et al. Effects of fullerenes and single-wall carbon nanotubes on murine and human macrophages. Carbon 2006; 44(6):1100–1105.

    Article  CAS  Google Scholar 

  66. Lin YL, Lei HY, Wen YY et al. Light-dependent inactivation of Dengue-2 virus by carboxyfullerene C60 isomer. Virology 2000; 275:258–62.

    Article  PubMed  CAS  Google Scholar 

  67. Straface E, Natalini B, Monti D et al. C3-Fullero-tris-methanodicarboxylic acid protects epithelial cells from radiation-induced anoikia by influencing cell adhesion ability. FEBS Lett 1999; 454:335–40.

    Article  PubMed  CAS  Google Scholar 

  68. Monti D, Moretti L, Salvioli S et al. C60 carboxyfullerene exerts a protective activity against oxidative stress-induced apoptosis in human peripheral blood mononuclear cells. Biochemical and Biophysical Research Communications 2000; 277:711–7.

    Article  PubMed  CAS  Google Scholar 

  69. Lin AM, Chyi BY, Wang SD et al. Carboxyfullerene prevents iron-induced oxidative stress in rat brain. Journal of Neurochemistry 1999; 72(4):1634–40.

    Article  PubMed  CAS  Google Scholar 

  70. Tsao N, Luh TY, Chou CK et al. Inhibition of group A streptococcus infection by carboxyfulleren. Antimicrobial Agents and Chemotherapy 2001; 1788-93.

    Google Scholar 

  71. Tsao N, Luh TY, Chou CK et al. In vitro action of carboxyfullerene. Journal of Antimicrobial Chemotherapy 2002; 49:641–9.

    Article  PubMed  CAS  Google Scholar 

  72. Sijbesma R, Srdanov G, Wudl F et al. Synthesis of a fullerenes derivative for the inhibition oh HIV enzymes. J Am Chem Soc 1993; 115:6510.

    Article  CAS  Google Scholar 

  73. Schinazi RF, McMillan A, Juodawlkis AS et al. Synthesis and virucidal activity of a water-soluble, configurationally stable, derivatized C60 Fullerene. Proc Electrochem Soc 1994; 94-24:689.

    CAS  Google Scholar 

  74. Yamakoshi Y, Yagami T, Sueyoshi S et al. Acridine adduct of [60]fullerenes with enhanced DNA-cleaving activity. The Journal of Organic Chemistry 1996; 61:7236–7.

    Article  PubMed  CAS  Google Scholar 

  75. Schinazi RF, Sijbesma R, Srdanov G et al. Synthesis and virucidal activity of a water-soluble, configurationally stable, derivatized C60 fullerene. Antimicrobial Agents and Chemotherapy 1993; 1707–10.

    Google Scholar 

  76. Huang HM, Ou HC, Hsieh SJ et al. Blockage of amyloid beta peptide-induced cytosolic free calcium by fullerenol-1, carboxylate C60 in PC12 cells. Life Science 2000; 66(16):1525–33.

    Article  CAS  Google Scholar 

  77. Bisaglia M, Natalini B, Pellicciari R et al. C3-fullero-tris-methanodicarboxylic acid protects cerebellar granule cells from apoptosis. Journal of Neurochemistry 2000; 74:1197–204.

    Article  PubMed  CAS  Google Scholar 

  78. Rancan F, Helmreich M, Molich A et al. Fullerene-pyropheophorbide a complexes as sensitizer for photodynamic therapy: Uptake and photo-induced cytotoxicity on Jurkat cells. J Photochem Photobiol B 2005; 80(1):1–7.

    Article  PubMed  CAS  Google Scholar 

  79. Chueh SC, Lai MK, Chen SC et al. Chiang Fullerenols in canine renal preservation-A preliminary report. Kidney 1997; 1313–5.

    Google Scholar 

  80. Lai YL, Chiang LY. Water-soluble fullerene derivatives attenuate exsanguination-induced bronchoconstriction of guinea-pigs Journal of Autonomic Pharmacology 1997; 17:229–35.

    Article  PubMed  CAS  Google Scholar 

  81. Chen HH, Yu C, Ueng TH et al. Acute and subacute toxicity study of water-soluble polyalkylsulfonated C60 in rats. Toxicol Pathol 1998; 26(1):143–51.

    Article  PubMed  CAS  Google Scholar 

  82. Huang SS, Tsai SK, Chih CL et al. Neuroprotective effect of hexasulfobutylated C60 on rats subjected to focal cerebral ischemia. Free Radical Biology and Medicine 2001; 30(6):643–9.

    Article  PubMed  CAS  Google Scholar 

  83. Yang DY, Wang MF, Chen IL et al. Systemic administration of a water-soluble hexasulfonated C(60) (FC(4)S) reduces cérébral ischemia-induced infarct volume in gerbils. Neuroscience Letters 2001; 311:121–4.

    Article  PubMed  CAS  Google Scholar 

  84. Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005; 113(7):823–39.

    PubMed  CAS  Google Scholar 

  85. Hans C, Fischer HC, Liu L et al. Pharmacokinetics of nanoscale quantum dots: In vivo distribution, sequestration, and clearance in the rat. Adv Funct Mater 2006; 16:1299–1305.

    Article  CAS  Google Scholar 

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Kolosnjaj, J., Szwarc, H., Moussa, F. (2007). Toxicity Studies of Fullerenes and Derivatives. In: Chan, W.C.W. (eds) Bio-Applications of Nanoparticles. Advances in Experimental Medicine and Biology, vol 620. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76713-0_13

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