PHARMACOPHORE SUPERFAMILY TO OPERATE THE CELL PROLIFERATION AND APOPTOSIS PROCESSES

PHARMACOPHORE SUPERFAMILY TO OPERATE THE CELL PROLIFERATION AND APOPTOSIS PROCESSES

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Author(s)

Author(s): Prof. Marina A. Orlova

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1104 1732 Volume 1 - Oct 2012

Abstract

Fullerene derivatives superfamily attracts a serious attention of pharmacologists since some of these variable agents were proven to be not only drug delivery carriers but anti - cancer and immunomodulators as well. Most specifically, photodynamic therapy of malignant tumors is known for the fullerenes engagement. However, there is an obvious deficit of information on the cellular and molecular mechanisms of the fullerenes pharmacological effects which is a true obstacle on the way leading to practical medicinal use of the latters. Particularly, the mode of both direct (immediate) and distant side effects origin along with a fullerenes impact on necrosis, apoptosis and cell proliferation processes are no doubt needed to get far more clearified. It is hardly possible to exaggerate a significance of the fullerene nanoparticles functionalization type, their sizes and surface nanotopology for further promoting of either cytoprotective or cytotoxic effects. Noteworthy, the antioxidant properties of some water soluble fullerene derivatives were revealed while the fullerenes induced ROS formation might be also occurred. One of the most intriguing peculiarity of the fullerenes as pharmacophores consists in capabilities of some of them to intervene into the structure domains of functional proteins including enzymes and organelles linked receptors as well as to play a role of intercalators interacting with DNA double helix which, in turn, leads to a number of crucial consequences such as the biopolymer conformational flexibility shifts, catalytic activity changes, ligand docking affinity impacts in cell signaling pathways. Last not least, the fullerens are about to compete with several natural metabolites and effectots which is itself a valid platform for pharmacological outreach. This Review deals with an Authors’s original attempt to analyse the above mentioned points with an aim to elucidate those properties, methodological and structural, of numerous fullerene adducts that determine their apoptosis- and cell proliferation – modulating effects with a special respect to a target cell / tumor type.

Keywords

fullerenes, signaling pathways, oxidative stress, cancer treatment, apoptosis control, targeted drug delivery

References

  1. Duncan, R.; Gaspar, R. Nanomedicine(s) under the microscope. Mol. Pharmaceutics, 2011, 8, 2101–2141
  2. Kateb, B.; Chiu, K.; Black, K.L.; Yamamoto, V.; Khalsa, B.; Ljubimova, J.Y.; Ding, H.; Patil, R.; Portilla-Arias, J.A.; Modo, M.; Moore, D.F.; Farahani, K.; Okun, M.S.; Prakash, N.; Neman, J.; Ahdoot, D.; Grundfest, W.; Nikzad, S.; Heiss, J.H. Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy? NeuroImage, 2011, 54, S106-S124
  3. Harhaji, L.; Isakovic, A.; Raicevic, N.; Markovic, Z.; Todorovic-Markovic, B.; Nikolic, N.; Vranjes-Djuric, S.; Markovic, I.; Trajkovic, V. Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. Eur. J. Pharmacol., 2007, 568, 89-98
  4. Dugan, L.L.; Turetsky, D.M.; Du, C.; Lobner, D.; Wheeler, M.; Almli, R.; Shen, C.K.F.; Luh, T.Y.; Choi, D.W.; Lin, T.S. Carboxyfullerenes as neuroprotective agents. Proc. Natl. Acad. Sci. U.S.A, 1997, 94, 9434-9439.
  5. Monti, D.; Moretti, L.; Salvioli, S.; Strafolacince, E.; Malorni, W.; Pellicciari, R.; Schettini, G.; Bisaglia, M.; Pincelli, C.; Fumelli, C.; Bonafe, M.; Franceschi, C. C60 carboxyfullerene exerts a protective activity against oxidative stress-induced apoptosis in human peripheral blood mononuclear cells. Biochem. Biophys. Res. Commun., 2000, 277, 711-717
  6. Dugan, L.L.; Gabrielsen, J.K.; Yu, S.P.; Lin, T.S.; Choi, D.W. Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiol. Dis., 1996, 3, 129-135
  7. Isakovic, A.; Markovic, Z.; Nikolic, N.; Todorovic-Markovic, B.; Vranjes-Djuric, S.; Harhaji, L.; Raicevic, N.; Romcevic, N.; Vasiljevic-Radovic, D.; Dramicanin, M.; Trajkovic, V. Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation. Biomaterials, 2006, 27, 5049-5058
  8. Isakovic, A.; Markovic, Z.; Todorovic-Markovic, B.; Nikolic, N.; Vranjes-Djuric, S.; Mirkovic, M.; Dramicanin, M.; Harhaji, L.; Raicevic, N.; Nikolic, Z.; Trajkovic, V. Distinct cytotoxic mechanisms of pristine versus hydroxylated fullerene. Toxicol. Sci., 2006, 91, 173–183
  9. Yamawaki, H.; Iwai, N. Cytotoxicity of water-soluble fullerene in vascular endothelial cells. Am. J. Physiol. Cell Physiol., 2006, 290, C1495–C1502
  10. Yang, X.L.; Fan, C.H.; Zhu, H.S. Photo-induced cytotoxicity of malonic acid [C60]fullerene derivatives and its mechanism. Toxicol. InVitro, 2002, 16, 41–46
  11. Rancan, F.; Rosan, S.; Boehm, F.; Cantrell, A.; Brellreich, M.; Schoenberger, H.; Hirsch, A.; Moussa, F. Cytotoxicity and photocytotoxicity of a dendritic C60 mono-adduct and a malonic acid C60 tris-adduct on Jurkat cells. J. Photochem. Photobiol., B., 2002, 67, 157–162
  12. Bosi, S.; L.Feruglio, L.; T.Da Ros, T.; G.Spalluto, G.; B.Gregoretti, B.; M.Terdoslavich, M. Hemolytic effects of water-soluble fullerene derivatives. J. Med. Chem., 2004, 47, 6711-6715
  13. Tabata, Y.; Ishii, T.; Aoyama, T.; Oki, R.; Hirano, Y.; Ogawa, O.; Ikada, Y. In: Perspectives of Fullerene Nanotechnology. Ed. E.Osawa, Kluwer Academic Publ., Dordrecht; Boston; London, 2001
  14. Chen, C.; Xing, G.; Wang, J.; Zhao, Y.; Li, B.; Tang, J.; Jia, G.; Wang, T.; Sun, J.; Xing, L.; Yuan, H.; Gao, Y.; Meng, H.; Chen, Z.; Zhao, F.; Chai, Z.; Fang, X. Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity. .Nano Lett., 2005, 5, 2050–2057
  15. Darwish, A.D. Fullerenes. Annu. Rep. Prog. Chem., A, 2010, 106, 356–375
  16. Shirinkin, S.V.; Volkova, T.O.; Nemova, N.N. In: “Medicinal nanotechnology. The using of fullerenes in a therapy of respiratory diseases”, Ed. Karelsky Sci. Centre RAS, Petrazavodsk. 2009
  17. Gao, J.; Wang, H.L.; Shreve, A.; Iyer, R. Fullerene derivatives induce premature senescence: A new toxicity paradigm or novel biomedical applications, Toxicol. Appl. Pharmacol., 2010, 244, 130–143
  18. Jung, H.; Wang, C.; Jang, W. Nano-C60 and hydroxylated C60: Their impacts on the environment, Toxicol. Environ. Health Sci., 2009, 1, 132-139
  19. Sidorov, L.N.; Yurovskaya, M.A.; Borschevsky, A.Ya.; Trushkov, I.V.; Ioffe, I.N. Fullerenes, Ed. Examination, Moscow. 2005
  20. Hirsch, A.; Brettreich, M. Fullerenes: chemistry and reactions. Wiley-VCH, Weinheim. 2005
  21. Piotrovsky, L.B. Fullerenes in biology. Ed. Rostock. St. Petersburg. 2006
  22. Troshin, P.A.; Lyubovskaya, Z.N. Organic chemistry of fullerenes: basic reaction, types of fullerene compounds and prospects for their practical application. Adv. Chem. (Russ), 2008, 77, 324-369
  23. Ema, M.; Kobayashi, N.; Naya, M.; Hanai, S.; Nakanishi, Reproductive and developmental toxicity studies of manufactured nanomaterials. J. Reprod. Toxicol., 2010, 30, 343-352
  24. Markovic, Z.; Trajkovic, V. Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C60). Biomaterials, 2008, 29, 3561-3573
  25. Grausova, L.; Vacik, J.; Vorlicek, V.; Svorcik, V.; Slepicka, P.; Bilkova, P.; Vandrovcova, M.; Lisa, V.; Bacakovа, L. Fullerene C60 films of continuous and micropatterned morphology as substrates for adhesion and growth of bone cells. Diamond Relat. Mater., 2009, 18, 578-586
  26. Aschberger, K.; Johnston, H.J.; Stone, V.; Aitken, R.J.; Tran, C.L.; Hankin, S.M.; Peters, S.A.; Christensen, F.M. Review of fullerene toxicity and exposure – Appraisal of a human health risk assessment, based on open literature. Regul. Toxicol. Pharmacol., 2010, 58, 455-473
  27. Da Ros, T.; Spalluto, G.; Prato, M. Biological applications of fullerene derivatives: a brief overview. Croat. Chem. Acta, 2001, 74, 743-755
  28. Da Ros, T. Twenty Years of Promises: Fullerene in Medicinal Chemistry. Carbon Mater.: Chem. Phys., 2008, 1, 1-21
  29. Bakry, R.; Vallant, R.M.; Najam-ul-Haq, M.; Rainer, M.; Szabo, Z.; Huck, C.; Bonn, G.K. Medicinal applications of fullerenes. Int. J. Nanomed., 2007, 4, 639–649
  30. Satoh, M.; Takayanagi, I. Pharmacological Studies on Fullerene (C60), a Novel Carbon Allotrope, and Its Derivatives. J. Pharmacol. Sci., 2006, 100, 513-518
  31. Chawla, P.; Chawla, V.; Maheshwari, R.; Saraf, A.; Saraf, K. Fullerenes: from carbon to nanomedicine. Mini Reviews in Med. Chem., 2010, 10, 662-677
  32. Partha, R.; Conyers, J.L. Biomedical applications of functionalized fullerene-based nanomaterials. Int. J. Nanomed., 2009, 4, 261–275
  33. Yan, L.; Zhao, F.; Li, S.; Hu, Z.; Zhao, Y. Low-toxic and safe nanomaterials by surface-chemical design, carbon nanotubes, fullerenes, metallofullerenes, and graphenes. Nanoscale, 2011, 3, 362–382
  34. Parveen, S.; Misra, R.; Sahoo, S.K. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine: Nanotechnol. Biol. Med., 2012, 8, 147-166
  35. Huh, A.J.; Kwon, Y.J. “Nanoantibiotics”: A new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J. Control. Release, 2011, 7, 128-145
  36. Koifman, O.I.; Mamardashvili, I.Z.; Antipin, I.S. Synthetic receptors based on porphyrins and their conjugates with kliks [4] arenes, Ed. Nauka, Moscow. 2006
  37. Satake, A.; Kobuke, Y. Dynamic supramolecular porphyrin system. Tetrahedron, 2005, 61, 13-41
  38. Tykhomyrov, A.A.; Nedzvetsky, V.S.; Klochkov, V.K.; Andrievsky,G.V. Nanostructures of hydrated C60 fullerene (C60HyFn) protect rat brain against alcohol impact and attenuate behavioral impairments of alcoholized animals.. Toxicology, 2008, 246, 158-165
  39. Spohn, P.; Hirsch, C.; Hasler, F.; Bruinink, A.; Krug, H.F.; Wick, P. C60 fullerene: a powerful antioxidant or a damaging agent? The importance of an in-depth material characterization prior to toxicity assays. Environ. Pollut., 2009, 157, 1134–1139
  40. Yokel, R.A.; MacPhail, R.C. Engineered nanomaterials: exposures, hazards, and risk prevention. J. Occup. Med. Toxicol., 2011, 6, 7-34
  41. Buseck, P.R. Geological fullerenes: review and analysis. Earth Planet. Sci. Lett., 2002, 203, 781-792
  42. Shinohara, N.; Gamo, M.; Nakanishi, J. Fullerene C60: inhalation hazard assessment and derivation of a period-limited acceptable exposure level. Toxicol. Sci., 2011, 123, 576-589
  43. Orlova, M.A.; Orlov, A.P. Role of zinc in an organism and its influence on processes leading to apoptosis. Br. J. Med. Med. Res., 2011, 1, 239-305
  44. Portt, L.; Norman, G.; Clapp, C.; Greenwood, M. Anti-apoptosis and cell survival. Biochim. Biophys. Acta, 2011, 1813, 238-259
  45. Shvedova, A.A.; Kagan, V.E.; Fadeel, B. Close encounters of the small kind: adverse effects of man-made materials interfacing with the nano-cosmos of biological systems. Annu. Rev. Pharmacol. Toxicol., 2010, 50, 63-88
  46. Usenko, C.Y.; Harper, S.L.; Tanguay, R.L. Fullerene C60 exposure elicits an oxidative stress response in embryonic zebrafish. Toxicol. Appl. Pharmacol., 2008, 229, 44-55
  47. Yamakoshi, Y.; Umezawa, N.; Ryu, A.; Arakane, K.; Miyata, N.; Goda, Y. Active oxygen species generated from photoexcited fullerene (C60) as potential medicines: O2.-- versus 1O2. J. Am. Chem. Soc., 2003, 125, 12803-12809
  48. Scrivens, W.A.; Tour, J.M.; Creek, K.E.; Pirisi, L. Synthesis of 14C-labeled C60, its suspension in water, and its uptake by human keratinocytes. J. Am. Chem. Soc., 1994, 116, 4517-4518
  49. Maeda, R.; Noiri, E.; Isobe, H.; Homma, T.; Tanaka, T.; Negishi, K.; Doi, K.; Fujita, T.; Nakamura, E. A water-soluble fullerene vesicle alleviates angiotensin II-induced oxidative stress in human umbilical venous endothelial cells. Hypertension Res., 2008, 31, 141-151
  50. Fortner, J.D.; Lyon, D.Y.; Sayes, C.M.; Boyd, A.M.; J.C.Falkner, J.C.; E.M.Hotze, E.M.; L.B.Alemany, L.B.; Y.J.Tao, Y.J.; Guo, W.; Ausman, K.D.; Colvin, V.L.; Hughes, J.B. C-60 in water: nanocrystal formation and microbial response. Environ. Sci. Technol., 2005, 39, 4307–4316
  51. Henry, T.B.; Menn, F.M.; Fleming, J.T.; Wilgus, J.; Compton, R.N.; Sayler, G.S. Attributing effects of aqueous C-60 nano-aggregates to tetrahydrofuran decomposition products in larval zebrafish by assessment of gene expression. Environ. Health Perspect., 2007, 115, 1059–1065
  52. Colvin, V.L. The potential environmental impact of engineered nanomaterials. Nat. Biotechnol., 2003, 21, 1166-1170
  53. Sayes, C.M.; Gobin, A.M.; Ausman, K.D.; Mendez, J.; West, J.; Colvin, V.L. Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials, 2005, 26, 7587-7595
  54. Oberdorster, E.; Zhu, S.; Blickley, T.; McClellan-Green, P.; Haasch, M. Ecotoxicology of carbon-based engineered nanoparticles: effects of fullerene (C60) on aquatic organisms. Carbon, 2006, 44, 1112-1120
  55. Andrievsky, G.; Klochkov, V.; Derevyanchenko, L. Is the C60 fullerene molecule toxic?! Fullerenes Nanotubes Carbon Nanostructures, 2005, 13, 363-376
  56. Andrievsky, G.; Klochkov, V.; Bordyuh, A.; Dovbeshko, G. Comparative analysis of two aqueous–colloidal solutions of C60 fullerene with help of FTIR reflectance and UV–vis spectroscopy. Chem. Phys. Lett., 2002, 364, 8-17
  57. Gharbi, N.; Pressac, M.; Hadchouel, M.; Szwarc, H.; Wilson, S.R.; Moussa, F. [60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett., 2005, 5, 2578-2585
  58. Kolosnjaj, J.; Szwarc, H.; Moussa, F. Toxicity studies of fullerenes and derivatives. Adv. Exp. Med. Biol., 2007, 620, 168-180
  59. Jia, G.; Wang, H.; Yan, L.; Wang, X.; Pei, R.; Yan, T.; Zhao, Y.; Guo, X. Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. Environ. Sci. Technol., 2005, 39, 1378–1383
  60. Sayes, C.M.; Marchione, A.A.; Reed, K.L.; Warheit, D.B. Comparative pulmonary toxicity assessments of C60 water suspensions in rats: few differences in fullerene toxicity in vivo in contrast to in vitro profiles. Nano Lett., 2007, 7, 2399-2406
  61. Baker, G.L.; Gupta, A.; Clark, M.L.; Valenzuela, B.R.; Staska, L.M. Inhalation toxicity and lung toxicokinetics of C60 fullerene nanoparticles and microparticles. Toxicol. Sci., 2008, 101, 122-131
  62. Horie, M.; Nishio, K.; Kato, H.; Shinohara, N.; Nakamura, A.; Fujita, K.; Kinugasa, S.; Endoh, S.; Yamamoto, K.; Yamamoto, O.; Niki, E.; Yoshida, Y.; Iwahashi, H. In vitro evaluation of cellular responses induced by stable fullerene C60 medium dispersion. J. Biochem., 2010, 148, 289-298
  63. Osuna, S.; Swart, M.; Solà, M. On the Mechanism of action of fullerene derivatives in superoxide dismutation. Chemistry – Eur. J., 2010, 16, 3207-3214
  64. Zhou, S.; Burger, C.; Chu, B.; Sawamura, M.; Nagahama, N.; Toganoh, M. Spherical bilayer vesicles of fullerene-based surfactants in water: a laser light scattering study. Science, 2001, 291, 1944-1947
  65. Sawamura, M.; Kawai, K.; Matsuo, Y.; Kanie, K.; Kato, T.; Nakamura, E. Stacking of conical mesogens with a fullerene apex into polar columns in crystals and liquid crystals. Nature, 2002, 419, 702-705
  66. Yin, J.J.; Lao, F.; Fu, P.P.; Wamer, W.G.; Zhao, Y.; Wang, P.C. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials, 2009, 30, 611-621
  67. Tokuyama, H.; Yamago, S.; Nakamura, E.; Shiraki, T.; Sugiura, Y. Photoinduced biochemical-activity of fullerene carboxylic-acid. J. Am. Chem. Soc., 1993, 115, 7918–7919
  68. Husebo, L.O.; Sitharaman, B.; Furukawa, K.; Kato, T.; Wilson, L.J. Fullerenols revisited as stable radical anions. J. Am. Chem. Soc., 2004, 126, 12055-12064
  69. Yamakoshi, Y.N.; Yagami, T.; Sueyoshi, S.; Miyata, N. Acridine adduct of [60]fullerene with enhanced DNA-cleaving activity. J. Org. Chem., 1996, 61, 7236–7237
  70. Andersson, T.; Nilsson, K.; Sundahl, M.; Westman, G.; Wennerstrom, O. C60 embedded in gamma-cyclodextrin—a water-soluble fullerene. J. Chem. Soc. Chem. Commun. 1992, 8, 604–606
  71. Makha, M.; Purich, A.; Raston, C.L.; Sobolev, A.N. Structural diversity of host-guest and intercalation complexes of fullerene C60. Eur. J. Inorg. Chem., 2006, 507-517
  72. Deguchi, S.; Mukai, S.A.; Tsudome, M.; Horikoshi, K. Facile generation of fullerene nanoparticles by hand-grinding. Adv. Mater., 2006, 18, 729-732
  73. Quaranta, A.; Zhang, Y.; Filippone, S.; Yang, J.; Sinay, P.; Rassat, A.; Edge, R.; Navaratnam, S.; McGarvey, D.; Land, E.J.; Brettreich, M.; Hirsch, A.; Bensasson, R.V. Photophysical studies of six amphiphilic 2:1 cyclodextrin:[60]fullerene derivatives. Chem. Phys., 2006, 325, 397–403
  74. Dhawan, A.; Taurozzi, J.S.; Pandey, A.K.; Shan, W.Q.; Miller, S.M.; Hashsham, S.A.; Tarabara, V.V. Stable colloidal dispersions of C60 fullerenes in water: evidence for genotoxicity. Environ. Sci. Technol. 2006, 40, 7394–7401
  75. Deguchi, S.; Alargova, R.G.; Tsujii, K. Stable dispersions of fullerenes, C60 and C70, in water: preparation and characterization. Langmuir, 2001, 17, 6013–6017
  76. Lyon, D.Y.; Adams, L.K.; Falkner, J.C.; Alvarez, P.J. Antibacterial activity of fullerene water suspensions: effects of preparation method and particle size. Environ. Sci. Technol., 2006, 40, 4360-4366
  77. Brant, J.A.; Labille, J.; Bottero, J.Y.; Wiesner, M.R. Characterizing the impact of preparation method on fullerene cluster structure and chemistry. Langmuir, 2006, 22, 3878–3885
  78. Shinohara, N.; Matsumoto, K.; Endoh, S.; Maru, J.; Nakanishi, J. In vitro and in vivo genotoxicity tests on fullerene C60 nanoparticles. Toxicol. Lett., 2009, 191, 289-296
  79. Seki, M.; Fujishima, S.; Gondo, Y.; Inoue, Y.; Nozaka, T.; Suemura, K.; Takatsuki, M. Acute toxicity of fullerene C60 in aquatic organism. Environ. Sci., 2008, 21, 53–62
  80. Cook, S.M.; Aker, W.G.; Rasulev, B.F.; Hwang, H.M.; Leszczynski, J.; Jenkins, J.; Shockley, V. Choosing safe dispersing media for C60 fullerenes by using cytotoxicity tests on the bacterium Escherichia coli. J. Hazard Mater., 2010, 176, 367-373
  81. Cho, M.; Fortner, J.D.; Hughes, J.B.; Kim, J.H. Escherichia coli inactivation by water-soluble, ozonated C60 derivative: kinetics and mechanisms. Environ. Sci. Technol., 2009, 43, 7410–7415
  82. Bosi, S.; Da Ros, T.; Spalluto, G.; Prato, M. Fullerene derivatives: an attractive tool for biological applications. Eur. J. Med. Chem., 2003, 38, 913-923
  83. Brettreich, M.; Hirsch, A. A highly water-soluble dendro[60]fullerene. Tetrahedron Lett. 1998, 39, 2731-/2734
  84. Markovic, Z.; Todorovic-Markovic, B.; Kleut, D.; Nikolic, N.; Vranjes-Djuric, S.; Misirkic, M.; Vucicevic, L.; Janjetovic, K.; Isakovic, A.; Harhaji, L.; Babic-Stojic, B.; Dramicanin, M.; Trajkovic, V. The mechanism of cell-damaging reactive oxygen generation by colloidal fullerenes. Biomaterials, 2007, 28, 5437-5448
  85. Karkischenko, N.N. Nanosafly: new approaches to risk assessment and toxicity of nanomaterials. Biomedicine (Russ), 2009, #1, 5-27
  86. Nishimura, T.; Kubota, R.; Tahara, M.; Nagaoka-Hamano, M.; Shimizu, K.; Hirose, A.; Tokunaga, H. Biological effects of fullerene C60 in mouse embryonic stem cells. Toxicol. Lett., 2006, 164S, S214
  87. Morimoto, Y.; Hirohashi, M.; Ogami, A.; Oyabu, T.; Myojo, T.; Nishi, K.; Kadoya, C.; Todoroki, M.; Yamamoto, M.; Murakami, M.; Shimada, M.; Wang, W.; Yamamoto, K.; Fujita, K.; Endoh, S.; Uchida, K.; Shinohara, N.; Nakanishi, J.; Tanaka, I. Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies. Part. Fibre Toxicol., 2010, 7, 4-22
  88. Giust, D.; Leon, D.; Ballesteros-Yanez, I.; Da Ros, T.; Albasanz, J.L.; Martín, M. Modulation of adenosine receptors by [60]fullerene hydrosoluble derivative in SK-N-MC cells. ACS Chem. Neurosci., 2011, 2, 363–369
  89. Trpkovic, A.; Todorovic-Markovic, B.; Kleut, D.; Misirkic, M.; Janjetovic, K.; Vucicevic, L.; Pantovic, A.; Jovanovic, S.; Dramicanin, M.; Marcovic, Z.; Trajkovic, V. Oxidative stress-mediated hemolytic activity og solvent exchange-prepared fullerene (C60) nanoparticles. Nanotechnol.,2010, 21, 375102
  90. Costa, C.L.A.; Chaves, I.S.; Ventura-Lima, J.; Ferreira, J.L.R.; Ferraz, L.; de Carvalho, L.; Monserrat, J.M. In vitro evaluation of co-exposure of arsenium and an organic nanomaterial (fullerene, C60) in zebrafish hepatocytes. Comp. Biochem. Physiol. C, 2012, 155, 206-212
  91. Sayes, С.; Fortner, J.; Guo, W.; Lyon, D.; Boyd, A.; Ausman, K.; Tao, Y.; Sitharaman, B.; Wilson, L.; Hughes, J.; West, J.; Colvin, V. The differential cytotoxicity of water soluble fullerenes. Nano Lett., 2004, 4, 1881-1887
  92. Lai, Y.L.; Murugan, P.; Hwang, K.C. Fullerene derivative attenuates ischemia-reperfusion-induced lung injury. Life Sci., 2003, 72, 1271-1278
  93. Kolesnichenko, A.V.; M.A.Timofeyev, M.A.; M.V.Protopopova, M.V. Toxicity of nanomaterials – 15 years of research. Russ. Nanotechnol. (Russ), 2008, 3, 54-61
  94. Hsu, H.C.; Chiang, Y.Y.; Chen, W.J.; Lee, Y.T. Water-soluble hexasulfobutyl-[60]-fullerene inhibits plasma lipid peroxidation by direct association with lipoproteins. J. Cardiovasc. Pharmacol., 2000, 36, 423-/427
  95. Lee, Y.T.; Chiang, L.Y.; Chen, W.J.; Hsu, H.C. Water-soluble hexasulfobutyl-[60]-fullerene inhibits low-density lipoprotein oxidation in aqueous and lipophilic phases. Proc. Soc. Exp. Biol. Med., 2000, 224, 69-75
  96. Hu, Z.; Guan, W.C.; Tang,X.Y.; Huang, L.Z.; Xu, H. Synthesis of water-soluble cystine C60 derivative with catalyst and its active oxygen radical scavenging ability. Chinese Chem. Lett., 2007, 18, 51-54
  97. Hu, Z.; Xing, H.P.; Zhu, Z.; Wang, W.; Guan, W.C. Synthesis of cystine C60 derivative and its protective effects on hydrogen peroxide-induced apoptosis in PC12 cells. Chinese Chem. Lett., 2007, 18, 145-148
  98. Hu, Z.; Guan, W.; Wang, W.; Huang, L.; Xing, H.; Zhu, Z. Protective effects of a novel cystine C60 derivative on hydrogen peroxide-induced apoptosis in rat pheochromocytoma PC12 cells. Chem. Biol. Interact., 2007, 167, 135-144
  99. Hu, Z.; Guan, W.; Wang, W.; Huang, L.; Tang, X.; Xu, H.; Zhu, Z.; Xie, X.; Xing, H. Synthesis of amphiphilic amino acid C60 derivatives and their protective effect on hydrogen peroxide-induced apoptosis in rat pheochromocytoma cells. Carbon, 2008, 46, 99-109
  100. Hu, Z.; Guan, W.; Wang, W.; Zhu, Z.; Wang, Y. Folacin C60 derivative exerts a protective activity against oxidative stress-induced apoptosis in rat pheochromocytoma cells. Bioorg. Med. Chem. Lett., 2010, 20, 4159-4162
  101. Hu, Z.; Liu, S.; Wei, Y.; Tong, E.; Cao, F.; Guan, W. Synthesis of glutathione C60 derivative and its protective effect on hydrogen peroxide-induced apoptosis in rat pheochromocytoma cells. Neurosci. Lett., 2007, 429, 81–86
  102. Ali, S.S.; Hardt, J.I.; Quick, K.L.; Kim-Han, J.S.; Erlanger, B.F.; Huang, T.T.; Epstein, C.J.; Dugan, L.L. A biologically effective fullerene (C60) derivative with superoxide dismutase mimetic properties. Free Radic. Biol. Med., 2004, 37, 1191–1202
  103. Wang, I.C.; Tai, L.A.; Lee, D.D.; Kanakamm,P.P.; Shen, C.K.; Luh, T.Y.; Cheng, C.H.; Hwang, K.C. C60 and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J. Med. Chem., 1999, 42, 4614-4620
  104. Guan, S.; Bao, Y.; Jiang, B.; An, L. Protective effect of protocatechuic acid from Alpinia oxyphyllaon hydrogen peroxide-induced oxidative PC12 cell death. Eur. J. Pharmacol., 2006, 538, 73-79
  105. Xiao, L.; H.Takada, H.; K.Maeda, K.; M.Haramoto, M.; N.Miwa, N. Antioxidant effects of water-soluble fullerene derivatives against ultraviolet ray or peroxylipid through their action of scavenging the reactive oxygen species in human skin keratinocytes. Biomed. Pharmacotherapy, 2005, 59, 351-358
  106. Tong, J.; Zimmerman, M.C.; Li, S.; Yi, X.; Luxenhofer, R.; Jordan, R.; Kabanov, A.V. Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation. Biomaterials, 2011, 32, 3654-3665
  107. Alcaraz, M.J.; Megıґas, J.; Garcıґa-Arnandis, I.; Cleґ rigues, V.; Guilleґn, M.I. New molecular targets for the treatment of osteoarthritis. Biochem. Pharmacol., 2010, 80, 13–21
  108. Bal, R.; Turk, G.; Tuzcu, M.; Yilmaz, O.; Ozercan, I.; Kuloglu, T.; Gur, S.; Nedzvetsky, V.S.; Tykhomyrov, A.A.; Andrievsky, G.V.; Baydas, G.; Naziroglu, M. Protective effects of nanostructures of hydrated C60 fullerene on reproductive function in streptozotocin-diabetic male rats. Toxicology, 2011, 282, 69-81
  109. Zhu, L.; Chang, D.W.; Dai, L.; Hong, Y. DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano. Lett., 2007, 3592-3597
  110. Xiao, L.; Aoshima, H.; Saitoh, Y.; Miwa, N. Highly hydroxylated fullerene localizes at the cytoskeleton and inhibits oxidative stress in adipocytes and a subcutaneous adipose-tissue equivalent. Free Radic. Biol. Med., 2011, 51, 1376–1389
  111. Mirkov, S.M.; Djordjevic, A.N.; Andric, N.L.; Andric, S.A.; Kostic, T.S.; Bogdanovic, G.M.; Vojinovic-Miloradov, M.B.; Kovacevic, R.Z. Nitric oxide-scavenging activity of polyhydroxylated fullerenol, C60(OH)24. Nitric Oxide, 2004, 11, 201-207
  112. Injac, R.; Perse, M.; Obermajer, N.; Djordjevic-Milic, V.; Prijatelj, M.; Djordjevic, A.; Cerar, A.; Strukelj, B. Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas. Biomaterials, 2008, 29, 3451–3460
  113. Bogdanovic, G.; Koji, V.; Dordevic, A.; Canadanovic-Brunet, J.; Vojinovic-Miloradov, M.; Balti, V.V. Toxicol. In Vitro, 2004, 18, 629-637. Modulating activity of fullerol C60(OH)22 on doxorubicin-induced cytotoxicity
  114. Wielgus, A.R.; Zhao, B.; Chignell, C.F.; Hu, D.N.; Roberts, J.E. Phototoxicity and cytotoxicity of fullerol in human retinal pigment epithelial cells. Toxicol. Appl. Pharmacol., 2010, 242, 79-90
  115. Inui, S.; Aoshima, H.; Nishiyama, A.; Itami, S. Improvement of acne vulgaris by topical fullerene application: unique impact on skin care. Nanomed. Nanotechnol. Biol. Med., 2011, 7, 238-241
  116. Mori, T.; Ito, S.; Namiki, M.; Suzuki, T.; Kobayashi, S.; Matsubayashi, K.; Sawaguchi, T. Involvement of free radicals followed by the activation of phospholipase A2 in the mechanism that underlies the combined effects of methamphetamine and morphine on subacute toxicity or lethality in mice: Comparison of the therapeutic potential of fullerene, mepacrine, and cooling, Toxicology, 2007, 236, 149-157
  117. Cagle, D.W.; Kennel, S.J.; Mirzadeh, S.; Alford, J.M.; Wilson, L.J. In vivo studies of fullerene-based materials using endohedral metallofullerene radiotracers. Proc. Natl. Acad. Sci. USA, 1999, 96, 5182-5187
  118. Oberdorster, E. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspect., 2004, 112, 1058-1062
  119. Lao, F.; Chen, L.; Li, W.; Ge, C.; Qu, Y.; Sun, Q.; Zhao, Y.; Han, D.; Chen, C. Fullerene nanoparticles selectively enter oxidation-damaged cerebral microvessel endothelial cells and inhibit JNK related apoptosis. AcsNano, 2009, 3, 3358-3368
  120. Rouzer, C.A, Nanopoarticle tumorigenicity. Chem. Res. Toxicol., 2010, 23, 4-5
  121. Podolsky, I.Ya.; Kondratieva, E.V.; Scheglov, I.V.; Dumpis, M.A.; Piotrovsky, L.B. C60 with polyvinylpyrrolidone to prevent violation of the formation of long-term memory. Solid State Physics (Russ), 2002, 44, 552-559
  122. Zaporotskova, I.V.; Chernozatonskiy, L.A. The mechanism the positive effect of fullerene on the recovery of spatial memory, Bull. New Med. Technol.(Russ.), 2005, 12, 117-119
  123. Dugan, L.L., Lovett, E.G.; Quick, K.L.; Lotharius, J.; Lin, T.T.; O’Malley, K.L. Fullerene-based antioxidants and neurodegenerative disorders. Parkinson. Relat. Disord., 2001, 7, 243-246
  124. Lin, J.; Wu, C. Surface characterization and platelet adhesion studies on polyurethane surface immobilized with C60. Biomaterials, 1999, 20, 1613-/1620
  125. Chen, T.; Li, Y.; Zhang, J.; Xu, B.; Lin, Y.; Wang, C.; Guan, W.; Wang, Y.; Xu, S. Protective effect of C60-methionine derivate on lead-exposed human SH-SY5Y neuroblastoma cells. J. Appl. Toxicol., 2011, 31, 255-261
  126. Linazasoro, G. Potential applications of nanotechnologies to Parkinson’s disease therapy. Parkinson. Relat. Disor., 2008, 14, 383-392
  127. Schloss, J.V.; Wu, J.Y. Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents. J. Neurosci. Res., 2000, 62, 600-607
  128. Lee, C.M.; Huang, S.T.; Huang, S.H.; Lin, H.W.; Tsai, H.P.; Wu, J.Y.; Lin, C.M.; Chen, C.T. C60 fullerene-pentoxifylline dyad nanoparticles enhance autophagy to avoid cytotoxic effects caused by the β-amyloid peptide. Nanomed. Nanotechnol. Biol. Med., 2011, 7, 107-114
  129. Szaraz, P.; Banhegyi, G.; Benedetti, A. Altered redox state of luminal pyridine nucleotides facilitates the sensitivity towards oxidative injury and leads to endoplasmic reticulum stress dependent autophagy in HepG2 cells. Int. J. Biochem. Cell Biol., 2010, 42, 157-166
  130. Hoyer-Hansen, M.; Bastholm, L.; Szyniarowski, P.; Campanella, M.; Szabadkai, G.; Farkas, T. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2. Mol. Cell, 2007, 25, 193-205
  131. Lu, T.; Kao, P.; Lee, C.; Huang, S.; Lin, C. C60 Fullerene nanoparticle prevents β-amyloid peptide induced cytotoxicity in neuro 2A cells. J. Food Drug Anal., 2011, 19, 151-158
  132. Podolski, I.Y.; Podlubnaya, Z.A.; Kosenko, E.A.; Mugantseva, E.A.; Makarova, E.G.; Marsagishvili, L.G. Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in vitro and performance of the cognitive task. J. Nanosci. Nanotechnol., 2007, 7, 1479-1485
  133. Brambilla, D.; Droumaguet, B.L.; Nicolas, J.; Hashemi, S.H.; Wu, L.P.; Moghimi, S.M.; Couvreur, P.; Andrieux, K. Nanotechnologies for Alzheimer's disease: diagnosis, therapy, and safety issues. Nanomed.: Nanotechnol. Biol. Med., 2011, 7, 521-540
  134. Lin, A.M.; Yang, C.H.; Ueng, Y.; Luh, T.Y.; Liu, T.Y.; Lay, Y.P.; Ho, L.T. Differential effects of carboxyfullerene on MPP+/MPTP-induced neurotoxicity. Neurochem. Int., 2004, 44, 99-105
  135. Hartig, W.; Paulke, B.R.; Varga, C.; Seeger, J.; Harkany, T.; Kacza, J. Electron microscopic analysis of nanoparticles delivering thioflavin-T after intrahippocampal injection in mouse: implications for targeting betaamyloid in Alzheimer’s disease. Neurosci. Lett., 2003,. 338, 174-176
  136. Gross, C.G. Neurogenesis in the adult brain: death of a dogma. Nature Rev. Neurosci., 2000, 1, 67-72
  137. Lebovits, R.; Rosenblum, M. Substuted fullerenes and their use as inhibitors of cell death. US Patent, #0197950 A1, 2009
  138. Friedman, S.H.; De Camp, D.L., Sijbesma, R.P.; Srdanov, G.; Wudl, F.; Kenyon, G.L. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J. Am. Chem. Soc., 1993, 115, 6506-6509
  139. Park, K.H.; Chhowalla, M.; Iqbal, Z.; Sesti, F. Single-walled carbon nanotubes are a new class of ion channel blockers. J. Biol. Chem., 2003, 278, 50212-50216
  140. Redmill, P.S.; McCabe, C. Molecular dynamics study of the behavior of selected nanoscale building blocks in a gel-phase lipid bilayer. J. Phys. Chem. B, 2010, 114, 9165-9172
  141. Kraszewski, S.; Tarek, M.; Treptow, W.; Ramseyer, C. Affinity of C60 neat fullerenes with membrane proteins: a computational study on potassium channels. ACSNano, 2010, 4, 4158–4164
  142. Orlova, M.A.; Osipova, E.Y.; Roumiantsev, S.A. Effect of 67Zn-nanoparticles on leukemic cells and normal lymphocytes. Br. J. Med. Med. Res., 2012, 2, 21-30
  143. Andreev, I.; Petrukhina, A.; Garmanova, A.; Babakhin, A.; Andreev, S.; Romanova, V.; Troshin, P.; Troshina, O.; DuBuske , L. Penetration of fullerene C60 derivatives through biological membranes. Fullerenes Nanotubes & Carbon Nanostructures, 2008, 16, 89-102
  144. Hsu, S.; Chien, C. Forced expression of Bcl-2 and Bcl-X(L) by novel water-soluble fullerene, C-60(glucosamine)(6), reduces renal ischemia/reperfusion-induced oxidative stress. Fullerene Sci. Technol., 2001, 9, 77-88
  145. Cha, Y.J.; Lee, J.; Choi, S.S. Apoptosis-mediated in vivo toxicity of hydroxylated fullerene nanoparticles in soil nematode Caenorhabditis elegans. Chemosphere, 2012, 87, 49-54
  146. Johnson, G.L.; Lapadat, R.L. Mitogen-activated protein kinase pathways mediated by ERK, JNK and p38 protein kinases. Science, 2002, 298, 1911-1912
  147. Fatkhutdinova, L.M.; Khaliullin, T.O.; Zalyalov, R.R. Toxicity of engineered nanoparticles. Kazanskii Med. J. (Russ.), 2009, 90, 578-584
  148. Manna, S.K.; Sarkar, S.; Barr, J.; Wise, K.; Barrera, E.V.; Jejelowo, O.; Rice-Ficht,| A.C.; Ramesh, G.T. Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-κB in human keratinocytes. Nano Lett., 2005, 5, 1676-1684
  149. Yudoh, K.; Karasawa, R.; Masuko, K.; Kato, T. Water-soluble fullerene (C60) inhibits the osteoclast differentiation and bone destruction in arthritis. Int. J. Nanomed., 2009, 4, 233-239
  150. Okada, T.; Otani, H.; Wu, Y.; Kyoi, S.; Enoki, C.; Fujiwara, H.; Sumida, T.; Hattori, R.; Imamura, H. Role of F-actin organization in p38 MAPkinase-mediated apoptosis and necrosis in neonatal rat cardiomyocytes subjected to simulated ischemia and reoxygenation. Am. J. Physiol. Heart Circ. Physiol., 2005, 289, H2310–H2318
  151. Luschen, S.; Scherer, G.; Ussat, S.; Ungefroren, H.; Adam-Klages, S. Inhibition of p38 mitogen-activated protein kinase reduces TNF-induced activation of NF-kB, elicits caspase activity, and enhances cytotoxicity. Exp. Cell Res., 2004, 293, 196–206
  152. Straface, E.; Natalini, B.; Monti, D.; Franceschi, C.; Schettini, G.; Bisaglia, M.; Fumelli, C.; Pincelli, C.; Pellicciari, R.; Malorni, W. C3-Fullero-tris-methanodicarboxylic acid protects epithelial cells from radiation-induced anoikia by influencing cell adhesion ability. FEBS Lett., 1999, 454, 335-340
  153. Johnson-Lyles, D.N.; Peifley, K.; Lockett, S.; Neun, B.W.; Hansen, M.; Clogston, J.; Stern, S.T.; McNeil, S.M. Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction. Toxicol. Appl. Pharmacol., 2010, 248, 249-258
  154. Rebecca, M.; Hsing-Lin, W.; Jun, G.; Srinivas, I.; Gabriel, M.A.; Jennifer, M.; Andrew, S.P.; Yuping, B.; Chun-Chih, W.; Zhong, C.; Yuan, G.; Rashi, I. Impact of physicochemical properties of engineered fullerenes on key biological responses. Toxicol. Appl. Pharmacol., 2009, 234, 58-67
  155. Zogovic, N.S.; Nikolic, N.S.; Vranjes-Djuric, S.D.; Harhaji, L.M.; Vucicevic, L.M.; Janjetovic, K.D.; Misirkic, M.S.; Todorovic-Markovic, B.M.; Markovic, Z.M.; Milonjic, S.K.; Trajkovic, V.S. Opposite effects of nanocrystalline fullerene (C60) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C60. Biomaterials, 2009, 30, 6940-6946
  156. Huang, Y.L.; Shen, C.K.F.; Luh, T.Y.; Yang, H.C.; Hwang, K.C.; Chou, C.K. Blockage of apoptotic signaling of transforming growth factor-beta in human hepatoma cells by carboxy-fullerene. Eur. J. Biochem., 1998, 254, 38-43
  157. Hsu, S.C.; Wu, C.C.; Luh, T.Y.; Chou, C.K.; Han, S.H.; Lai, M.Z. Apoptotic signal of Fas is not mediated by ceramide. Blood, 1998, 91, 2658-2663
  158. Li, W.; Zhao, L.; Wei, T.; Zhao, Y.; Chen, C. The inhibition of death receptor mediated apoptosis through lysosome stabilization following internalization of carboxyfullerene nanoparticles. Biomaterials, 2011, 32, 4030-4041
  159. Nakagawa, Y.; Suzuki, T.; Ishii, H.; Nakae, D.; Ogata, A. Cytotoxic effects of hydroxylated fullerenes on isolated rat hepatocytes via mitochondrial dysfunction. Arch. Toxicol., 2011, 85, 1429-1440
  160. Rouse, J.G.; Yang, J.Z.; Barron, A.R.; Monteiro-Riviere, N.A. Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes. Toxicol. in Vitro, 2006, 20, 1313-1320
  161. Huang, S.T.; Liao, J.S.; Fang, H.W.; Lin, C.M. Synthesis and anti-inflammation evaluation of new C60fulleropyrrolidines bearing biologically active xanthine. Bioorg. Med. Chem. Lett., 2008, 18, 99-103
  162. Gelderman, M.P.; Simakova, O.; Clogston, J.D.; Patri, A.K.; Siddiqui, S.F.; Vostal, A.C.; Simak, J. Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro. Int. J. Nanomed., 2008, 3, 59-68
  163. Zhu, J.; Ji, Z.; Wang, J.; Sun, R.; Zhang, X.; Gao, Y.; Sun, H.; Liu, Y.; Wang, Z.; Li, A.; Ma, J.; Wang, T.; Jia, G.; Gu, Y. Tumor-inhibitory effect and immunomodulatory activity of fullerol C60(OH)x. Small, 2008, 4, 1168–1175
  164. Harhaji, L.; Isakovic, A.; Vucicevic, L.; Janjetovic, K.; Misirkic, M.; Markovic, Z.; Todorovic-Markovic, B.; Nikolic, N.; Vranjes-Djuric, S.; Nikolic, Z,; Trajkovic, V. Modulation of tumor necrosis factor-mediated cell death by fullerenes. Pharm. Res., 2008, 25, 1365-1376
  165. Liu, R.L.; Cai, X.Q.; Wang, J.D.; Li, J.G.; Huang, Q.; Li, W.X. Research on the bioactivities of C60-dexamethasone. J. Nanosci. Nanotechnol., 2009, 9, 3171–3176
  166. Yang, D.; Zhao, Y.; Guo, H.; Li, Y.; Tewary, P.; Xing, G.; Hou, W.; Oppenheim, J.J.; Zhang, N. [Gd@C82(OH)22]n Nanoparticles induce dendritic cell maturation and activate Th1 immune responses. AcsNano, 2010, 4, 1178–1186
  167. Misirkic, M.S.; Todorovic-Markovic, B.M.; Vucicevic, L.M.; Janjetovic, K.D.; Jokanovic, V.R.; Dramicanin, M.D.; Markovic, Z.M.; Trajkovic, V.S. The protection of cells from nitric oxide-mediated apoptotic death by mechanochemically synthesized fullerene (C60) nanoparticles. Biomaterials, 2009, 30, 2319-2328
  168. Xu, A.; Chai, Y.; Nohmi, T.; Hei, T.K. Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells. Part. Fibre Toxicol., 2009, 6, 3-16
  169. Ciacci, L.C.C.; Vallottoc, D.; Galloa, G.; Marcominic, A.; Pojanac, G. In vitro effects of suspensions of selected nanoparticles (C60 fullerene, TiO2, SiO2) on Mytilus hemocytes. Aquatic Toxicol., 2010, 96, 151-158
  170. Fiorito, S.; Serafino, A.; Andreola, F.; Bernier, P. Effects of fullerenes and single-wall carbon nanotubes on murine and human macrophages, Carbon, 2006, 44, 1100-1105.
  171. Hu, Z.; Huang , Y.; Guan , W.; Zhang , J.; Wang , F.; Zhao, L. The protective activities of water-soluble C60 derivatives against nitric oxide-induced cytotoxicity in rat pheochromocytoma cells. Biomaterials , 2010, 31, 8872-8881
  172. Huang, S.S.; Tsai, S.K.; Chin, C.L.; Chiang, L.Y.; Hsieh, H.M.; Teng, C.M.; Tsai, M.C. Neuroprotective effect of hexasulfobutylated C60 on rats subjected to focal cerebral ischemia. Free Rad. Biol. Med., 2001, 30, 643-649
  173. Li, Y.; Liu, Y.; Fu, Y.; Wei, T.; Guyader, L.L.; Gao, G.; Liu, R.S.; Chang, Y.Z.; Chen, C. The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways. Biomaterials, 2012, 33, 402-411.
  174. Kotelnikova, R.A.; Kotelnikov, A.I.; Bogdanov, G.N.; Romanova, V.S.; Kuleshova, E.F.; Parnes, Z.N. Membranotropic properties of the water soluble amino acid and peptide derivatives of fullerene C60. FEBS Lett., 1996, 389, 111-114
  175. Chen, Y.W.; Hwang, K.C.H.; Yen, C.C.; Lai, Y.L. Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs. Am. J. Physiol., 2004, 287, 21-26
  176. Chien, C.T.; Chen, C.F.; Hsu, S.M.; Chiang, L.Y.; Lai, M.K. Forced expression of bcl-2 and bcl-xL by novel water-soluble fullerene, C60(glucosamine)6, reduces renal ischemia/reperfusion-induced oxidative stress. Fuller Nanotub Car., 2001, 9, 77-88
  177. Bisaglia, M.; Natalini, B.L.; Pellicciari, R.; Straface, E.; Malorni, W.; Monti, D. Carboxyfullerenes as neuroprotective agents C3-fullerotris-methanodicarboxylic acid protects cerebellar granule cells from apoptosis. J. Neurochem., 2000, 74, 1197-1204
  178. Nel, A.; Xia, T.; Madler, L.; Li, N. Toxic potential of materials at the nanolevel. Science, 2006, 311, 622-627
  179. Maynard, A.D.; Aitken, R.J.; Butz, T.; Colvin, V.; Donaldson, K.; Oberdorster, G.; Philbert, M.A.; Ryan, J.; Seaton, A.; Stone, V. Safe Handling of Nanotechnology. Nature, 2006, 444, 267-269
  180. Calvaresi, M.; Zerbetto, F. Baiting Proteins with C60. AcsNano. 2010, 4, 2283–2299
  181. Da Ros, T.; M.Prato, M.; F.Novello, F.; M.Maggini, M.; E.Banfi, E. Easy acess to water-soluble fullerene derivatives via 1,3-dipolar cycloadditions of azomethine ylides to C60. J. Org. Chem., 1996, 61, 9070-9072
  182. Jin, H.; Chen, W.Q.; Tang, X.W.; Chiang, L.Y.; Yang, C.Y.; Schloss, J.V.; Wu, J.Y. Polyhydroxylated C60, Fullerenols, as glutamate receptor antagonists and neuroprotective agents. J. Neurosci. Res., 2000, 62, 600-607
  183. Boutorine, A.S.; Tokuyama, H.; Takasugi, M.; Isobe, H.; Nakamura, E.; Helene, C. Fullerene-oligonucleotide conjugates: photoinduced sequence-specific DNA cleavage. Angew. Chem. Int. Ed., 1994, 33, 2426-2465
  184. Kim, J.E.; Lee, M. Fullerene inhibits β-amyloid peptide aggregation. Biochem. Biophys. Res. Commun., 2003, 303, 576-579
  185. Gupta, S.; Dhawan, A.; Shanker, R. In silico approaches: prediction of biological targets for fullerene derivatives. J. Biomed. Nanotechnol., 2011, 7, 91-92
  186. Wolff, D.J.; Barbieri, C.M.; Richardson, C.F.; Schuster, D.I.; Wilson, S.R. . Trisamine C60-fullerene adducts inhibit neuronal nitric oxide synthase by acting as highly potent calmodulin antagonists. Arch. Biochem. Biophys., 2002, 399, 130-141
  187. Mashino, T.; Okuda, K.; Hirota, T.; Hirobe, M.; Nagano, T.; Mochizuki, M. Inhibitory effect of fullerene derivatives on glutathione reductase. Fullerene Sci. Technol., 2001, 9, 191-196
  188. Marcorin, G.L.; Da Ros, T.; Castellano, S.; Stefancich, G.; Bonin, I.; Miertus, S.; Prato, M. Design and synthesis of novel [60]fullerene derivatives as potential HIV aspartic protease inhibitors. Org. Lett., 2000, 2, 3955-3958
  189. Schuster, D.I.; Wilson, S.R.; Schinazi, R.F, Anti-human immunodeficiency virus activity and cytotoxicity of derivatized Buckminsterfullerenes. Bioorg. Med. Chem. Lett., 1996, 6, 1253-1256
  190. Braden, B.C.; Goldbaum, F.A.; Chen, B.X.; Kirschner, A.N.; Wilson, S.R.; Erlanger, B.F. X-Ray crystal structure of an anti-Buckminsterfullerene antibody fab fragment: biomolecular recognition of C60. Proc. Natl. Acad. Sci. U.S.A., 2000, 97, 12193-12197
  191. Rozhkov, S.P.; Goryunov, A.S.; Sukhanova, G.A.; Borisova, A.G.; Rozhkova, N.N.; Andrievsky, G.V. Protein interaction with hydrated C60 fullerene in aqueous solutions. Biochem. Biophys. Res. Commun., 2003, 303, 562-566
  192. Belgorodsky, B.; Fadeev, L.; Kolsenik, J.; Gozin, M. Formation of a soluble stable complex between pristine C60-fullerene and a native blood protein. ChemBioChem., 2006, 7, 1783-1789
  193. Belgorodsky, B.; Fadeev, L.; Ittah, V.; Benyamini, H.; Zelner, S.; Huppert, D.; Kotlyar, A.B.; Gozin, M. Formation and characterization of stable human serum albumin-tris-malonic acid [C60]fullerene complex. Bioconjugate Chem., 2005, 16, 1058-1062
  194. Yang, S.T.; Wang, H.; Guo, L.; Gao, Y.; Liu, Y.; Cao, A. . Interaction of fullerenol with lysozyme investigated by experimental and computational approaches. Nanotechnology, 2008, 19, 395-401
  195. Benyamini, H.; Shulman-Peleg, A.; Wolfson, H.J.; Belgorodsky, B.; Fadeev, L.; Gozin, M. Interaction of C60-fullerene and carboxyfullerene with proteins: docking and binding site alignment. Bioconjugate Chem., 2006, 17, 378-386
  196. Zhang, X.F.; Shu, C.Y.; Xie, L.; Wang, C.; Zhang, Y.Z.; Xiang, J.F.; Li, L.; Tang, Y.L. Protein conformation changes induced by a novel organophosphate-containing water-soluble derivative of a C60 fullerene nanoparticle. J. Phys. Chem. C, 2007, 111, 14327-14333
  197. Belgorodsky, B.; Fadeeva, L.; Kolsenik, J.; Gozin, M. Biodelivery of a fullerene derivative. Bioconjugate Chem., 2007, 18, 1095-1100
  198. Ueng, T.H.; Kang, J.J.; Wang, H.W.; Cheng, Y.W.; Chiang, L.Y. Suppression of microsomal cytochrome P450-Dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C60. Toxicol. Lett., 1997, 93, 29-37
  199. Pastorin, G.; Marchesan, S.; Hoebeke, J.; Da Ros, T.; Ehret-Sabatier, L.; Briand, J.P.; Prato, M.; Bianco, A. Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesteras. Org. Biomol. Chem., 2006, 4, 2556-2562
  200. Innocenti, A.; Durdagi, S.; Doostdar, N.; Strom, T.A.; Barron, A.R.; Supuran, C.T. Nanoscale enzyme inhibitors: fullerenes inhibit carbonic anhydrase by occluding the active site entrance. Bioorg. Med. Chem., 2010, 18, 2822–2828
  201. Iwata, N.; T.Mukai, T.; Y.N.Yamakoshi, Y.N.; S.Hara, S.; T.Yanase, T.; M.Shoji, M.; T.Endo, T.; N.Miyata, N. Effect of C60, a fullerene, on the activities of glutathione S-transferase and glutathion-related enzymes. Fullerenes, Nanotubes & Carbon Nanostructures, 1998, 6, 213-226
  202. Marczak, R.; Hoang, V.T.; Noworyta, K.; Zandler, M.E.; Kutner, W.; D’Souza, F. Molecular recognition of adenine, adenosine and ATP at the air–water interface by a uracil appended fullerene. J. Mater. Chem., 2002, 12, 2123–2129
  203. Ito, M.; Nakashima, N. Design, synthesis and photophysical properties of C60-modified proteins. J. Mater. Chem., 2002, 12, 2026-2033
  204. Szeltukhin, A.O., Chumakov, P.M. Casual and induced functions of p53 gene. Success of Biol. Chem. (Russ.), 2010, 50, 447-516
  205. Liang, Y.; Luo, F.; Lin, Y.; Zhou, Q.F.; Jiang, G.B. C60 affects DNA replication in vitro by decreasing the melting temperature of DNA templates. Carbon, 2009, 47, 1457–1465
  206. Kang, F.; Song, G.G. Inhibition of Taq DNA polymerase and DNA exonuclease ExoIII by an aqueous nanoparticle suspension of a bis-methanophosphonate fullerene. Mater. Sci. Forum, 2011, 685, 345-351
  207. An, H.; Jin, B. DNA exposure to buckminsterfullerene (C60): toward DNA stability, reactivity, and replication. Environ. Sci. Technol., 2011, 45, 6608–6616
  208. Rohs, R.; West, S.M.; Sosinsky, A.; Liu, P.; Mann, R.S.; Honig, B. The role of DNA shape in protein-DNA recognition. Nature, 2009, 461, 1248–1253
  209. Pinteala, M.; Dascalu, A.; Ungurenasu, C. Binding fullerenol C60(OH)24 to dsDNA. Int. J. Nanomed., 2009, 4, 193-199
  210. Li, J.; Zhang, M.; Sun, B.; Xing, G.; Song, Y.; Guo, H.; Chang, Y.; Ge, Y.; Zhao, Y. Separation and purification of fullerenols for improved biocompatibility. Carbon, 2012, 50, 460-469
  211. Tanimoto, S.; Sakai, S.; Matsumura, S.; Takahashi, D.; Toshima, K. Target-selective photo-degradation of HIV-1 protease by a fullerene-sugar hybrid. Chem. Commun., 2008, 5767-5769
  212. Durdagi, S.; Mavromoustakos, T.; Chronakis, N.; Papadopoulos, M.G. Computational design of novel fullerene analogues as potential HIV-1 PR inhibitors: Analysis of the binding interactions between fullerene inhibitors and HIV-1 PR residues using 3D QSAR, molecular docking and molecular dynamics simulations. Bioorg. Med. Chem., 2008, 16, 9957-9974
  213. Bosi, S.; Da Ros, T.; Spalluto, G.; Balzarini, J.; Prato, M. Synthesis and anti-HIV properties of new water-soluble bis-functionalized [60]fullerene derivatives. Bioorg. Med. Chem. Lett., 2003, 13, 4437-4440
  214. Marchesan, S.; Da Ros, T.; Spalluto, G.; Balzarini, J.; Prato, M. Anti-HIV properties of cationic fullerene derivatives. Bioorg. Med. Chem. Lett., 2005, 15, 3615–3618
  215. Mashino, T.; Shimotohno, K.; Ikegami, N.; Nishikawa, D.; Okuda, R.; Takahashi, R.; Nakamura, S.; Mochizuki, M. Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg. Med. Chem. Lett., 2005, 15, 1107-1109
  216. Ungurenasu, C.; Pinteala, M. Syntheses and characterization of water-soluble C-60-Curdlan sulfates for biological applications. J. Polym. Sci. Polym. Chem., 2007, 45, 3124–3128
  217. Lehtovaara, B.C.; Gu, F.X. Pharmacological, structural, and drug delivery properties and applications of 1,3-β-glucans. J. Agric. Food Chem., 2011, 59, 6813–6828
  218. Shimanovsky, N.S. Nanotechnologies in contemporary pharmacology. Int. Med. J. (Russ.), 2009, â„–1, 131-135
  219. Fujita, K.; Morimoto, Y.; Ogami, A.; Myojyo, T.; Tanaka, I.; Shimada, M.; Wang, W.; Endoh, S.; Uchida, K.; Nakazato, T.; Yamamoto, K.; Fukui, H.; Horie, M.; Yoshida, Y.; Iwahashi, H.; Nakanishi, J. Gene expression profiles in rat lung after inhalation exposure to C60 fullerene particles. Toxicology, 2009, 258, 47-55
  220. Fujita, K.; Morimoto, Y.; Endoh, S.; Uchida, K.; Fukui, H.; Ogami, A.; Tanaka, I.; Horie, M.; Yoshida, Y.; Iwahashi, H.; Nakanishi, J. Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C60 fullerenes. Toxicology, 2010, 274, 34-41
  221. Xia, T.; Kovochich, M.; Brant, J.; Hotze, M.; Sempf, J.; Oberley, T.; Sioutas, C.; Yeh, J.I.; Wiesner, M.R.; Nel, A.N. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett., 2006, 6, 1794–1807
  222. Jacobsen, N.R.; Pojana, G.; White, P.; Møller, P.; Cohn, C.A.; Korsholm, K.S.; Vogel, U.; Marcomini, A.; Loft, S.; Wallin, H. Genotoxicity, cytotoxicity, and reactive oxygen species induced by single-walled carbon nanotubes and C60 fullerenes in the FE1-Muta™Mouse lung epithelial cells. Environ. Mol. Mutagen., 2008, 49: 476–487
  223. Jovanovic, B.; Ji, T.; Palic, D. Gene expression of zebrafish embryos exposed to titanium dioxide nanoparticles and hydroxylated fullerenes. Ecotoxicol. Environ. Safety, 2011, 74, 1518–1525
  224. Park, E.J.; Kim, H.; Kim, Y.; Yi, J.; Choi, K.; Park, K. Carbon fullerenes (C60s) can induce inflammatory responses in the lung of mice. Toxicol. Appl. Pharmacol., 2010, 244, 226-233
  225. Kaidashev, I.P. Influence of C60 fullerene on activity of phagocitic cells. Exp. Clinic. Pharmacol. (Russ.), 2011, #6, 26-29
  226. Xu, Y.; Zhu, J.; Xiang, K.; Li, Y.; Sun, R.; Ma, J.; Sun, H.; Liu, Y. Synthesis and immunomodulatory activity of [60]fullerene-tuftsin conugates. Biomaterials, 2011, 32(36), 9940-9949
  227. Vengerovich, N.G.; Tunin, M.A.; Antonenkova, E.V.; Konshakov, Yu.A.; Bolekhan, A.V.; Zaitseva, O.B.; Stukov, A.N.; Boyarkin, M.N.; Popov, V.A.. Biological activity of nanobiocomposites fullerene C60. Immonology (Russ), 2011, 12, 161-177
  228. Romoser, A.A.; Figueroa, D.E.; Sooresh, A.; Scribner, K.; Chen, P.L.; Porter, W.; Criscitiello, M.F.; Sayes, C.M. Distinct immunomodulatory effects of a panel of nanomaterials in human dermal fibroblasts. Toxicol. Lett., 2011, 6, 7-34
  229. Mrdanovic, J.; Solajic, S.; Bogdanoviс, V.; Stankov, K.; Bogdanovic, G.; Djordjevic, A. Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutation Res., 2009, 680, 25-30
  230. Nielsen, G.D.; Roursgaard, M.; Jensen, K.A.; Poulsen, S.S.; Larsen, S.T. Biology and toxicology of fullerenes and their derivatives. Basic Clin. Pharmacol. Toxicol., 2008, 103, 197–208
  231. Jalbout, A.F.; Hameed, A.J.; Trzaskowski, B. Study of the structural and electronic properties of 1-(4, 5 and 6-selenenyl derivatives-3-formyl-phenyl) pyrrolidinofullerenes, J. Organometal. Chem., 2007, 692, 1039-1047
  232. Jiao, F.; Liu, Y.; Qu, Y.; Li, W.; Zhou, G.; Ge, C.; Li, Y.; Sun, B.; Chen, C Studies on anti-tumor and antimetastatic activities of fullerenol in a mouse breast cancer model, Carbon, 2010, 48, 2231-2243
  233. Nishizawa, C.; Hashimoto, N.; Yokoo, S.; Funakoshi-Tago, M.; Kasahara, T.; Takahashi, K.; Nakamura, S.; Mashino, T. Pyrrolidinium-type fullerene derivative-induced apoptosis by the generation of reactive oxygen species in HL-60 cells, Free Radic. Res., 2009, 43, 1240–1247
  234. Wang, J.; C.Chen, C.; B.Li, B.; H.Yu, H.; Y.Zhao, Y.; J.Sun, J.; Y.Li, Y.; G.Xing, G.; H.Yuan, H.; J.Tang, J.; Z.Chen, Z.; H.Meng, H.; Y.Gao, Y.; C.Ye, C.; Z.Chai, Z.; C.Zhu, C.; B.Ma, B.; X.Fang, X.; L.Wanc, L. Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice, Biochem. Pharmacol., 2006, 71, 872-881
  235. Liu, Y.; Jiao, F.; Qiu, Y.; Li, W.; Qu, Y.; Li, Y. Immunostimulatory properties and enhanced TNF-a mediated cellular immunity for tumor therapy by C60(OH)20 nanoparticles, Nanotechnology, 2009, 20, 415102-415111
  236. Liu, Y.; Jiao, F.; Qiu, Y.; Li, W.; Lao, F.; Zhou, G.Q. The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-α mediated cellular immunity, Biomaterials, 2009, 30, 3934-3945
  237. Meng, H.; Xing, G.; Sun, B.; Zhao, F.; Lei, H.; Li, W.; Song, Y.; Chen, Z.; Yuan, H.; Wang, X.; Long, J.; Chen, C.; Liang, X.; Zhang, N.; Chai, Z.; Zhao, Y. Potent angiogenesis inhibition by the particulate form of fullerene derivatives. Acs Nano, 2010, 4, 2773-2783
  238. Darwish, A.D. Fullerenes, Annu. Rep. Prog. Chem., A, 2009, 105, 363–381
  239. Prylutska, S.; Burlaka, A.P.; Klymenko, P.P.; Grynyuk, I.I.; Prylutskyy, Yu.I.; Schütze, C.; Ritter, U. Using water-soluble C60 fullerenes in anticancer therapy, Cancer Nanotechnol., 2011, 2, 105-110
  240. Kharisov, B.I.; Kharissova, O.V.; Gomez, M.J.; Mendez, U.O. Recent advances in the synthesis, characterization, and applications of fulleropyrrolidines, Ind. Eng. Chem. Res., 2009, 48, 545–571
  241. Darwish, A.D. Fullerenes, Annu. Rep. Prog. Chem., A, 2007, 103, 370–391
  242. Mikawa, M.; Kato, H.; Okumura, M.; Narazaki, M.; Kanazawa, Y.; Miwa, N. Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents. Bioconjug. Chem., 2001, 12, 510-514
  243. Li, Q.; Xiu, Y.; Zhang, X.; Liu, R.; Du, Q.; Sun, X.; Chen, S.; Li, W. Biodistribution of fullerene derivative C60(OH)x(O)y, Chinese Sci. Bull., 2001, 46, 1615-1617
  244. Liu, J.H.; Cao, L.; Luo, P.G.; Yang, S.T.; Lu, F.; Wang, H.; Meziani, M.J.; Haque, S.A.; Liu, Y.; Lacher, S.; Sun, Y.P. Fullerene-conjugated doxorubicin in cells, Acs Appl. Mater. Interf., 2010, 2, 1384-1389
  245. Wei, P.; Zhang, L.; Lu, Y.; Man, N.; Wen, L. C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by modulation of autophagy, Nanotechnol., 2010, 21, 495101
  246. Montellano, A.; Da Ros , T.; Bianco, A.; Prato, M. Fullerene C60 as a multifunctional system for drug and gene delivery, Nanoscale, 2011, 3, 4035-4044
  247. Rancan, F.; Helmreich, M.; Molich, A.; Jux, N.; Hirsch, A.; Roder, B.; Witt, C.; Bohm, F. Fullerene-pyropheophorbide a complexes as sensitizer for photodynamic therapy: uptake and photo-induced cytotoxicity on Jurkat cells, J. Photochem. Photobiol. B, 2005, 80, 1-7
  248. Boyd, P.D.; Hodgson, M.C.; Rickard, C.E.F.; Oliver, A.G.; Chaker, L.; Brothers, P.J.; Bolskar, R.D.; Tham, F.S.; Reed, C.A. Selective supramolecular porphyrin/fullerene interactions, J. Am. Chem. Soc. 1999, 121, 10487-10495
  249. Sun, Y.; Drovetskaya, T.; Bolskar, R.D.; Bau, R.; Boyd, P.D.; Reed, C.A. Fullerides of pyrrolidine-functionalized C60, J. Org. Chem., 1997, 62, 3642-3649
  250. Imahori, H.; Mori, Y.; Matano, Y. . Nanostructured artificial photosynthesis, J. Photochem. Photobiol., C, 2003, 4, 51-83
  251. Da Ros, T.; Prato, M.; Guldi, D.M.; Ruzzi, M.; Pasimeni, L. Efficient charge separation in porphyrin-fullerene-ligand complexes, Chemistry, 2001, 7, 816-827
  252. Nishiyama, N.; Stapert, H.R.; Zhang, G.D.; Takasu, D.; Jiang, D.L.; Nagano, T.; Aida, T.; Kataoka, K. Light-harvesting ionic dendrimer porphyrins as new photosensitizers for photodynamic therapy, Bioconjugate Chem., 2003, 14, 58-66
  253. Dudic, M.; Lhotak, P.; Stibor, I.; Petrıckova, H.; Lang K. . (Thia)calyx[4]arene-porphyrin conjugates: novel receptors for fullerene complexation with C70 over C60 selectivity, New J. Chem., 2004, 28, 85-90
  254. Hirsch. A. The Chemistry of Fullerenes. Thieme-Verlag, Stuttgart; New York, 1994
  255. Rezayat, S.M.; Boushehri, S.V.S.; Salmanian, B.; Omidvari, A.H.; Tarighat, S.; Esmaeili, S.; Sarkar, S.; Amirshahi, N.; Alyautdin, R.N.; Orlova, M.A.; Trushkov, I.V.; Buchachenko, A.L.; Liu, K.C.; Kuznetsov, D.A. The porphyrin–fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect, Eur. J. Med. Chem., 2009, 44, 1554-1569
  256. Buchachenko, A.L.; Kuznetsov, D.A.; Breslavskaya, N.N.; Orlova, M.A. Magnesium Isotope Effect in Enzymatic Phosphorylation, J. Phys. Chem. B, 2008, 112, 2548-2556
  257. Nikolic, N.; Vranjes-Ethuric, S.; Jankovic, D.; Ethokic, D.; Mirkovic, M.; Bibic, N.; Trajkovic, V. Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals, Nanotechnol., 2009, 20, 385102.
  258. Ikeda, A.; Doi, Y.; Nishiguchi, K.; Kitamura, K.; Hashizume, M.; Kikuchi, J.; Yogo, K.; Ogawa, T.; Takey, T. Induction of cell death by photodynamic therapy with water-soluble lipid-membrane-incorporated [60]fullerene, Org. Biomol. Chem., 2007, 5, 1158–1160
  259. Wang, H.; Wang, L.; Wang, X.; Xu, J.; Luo, Q.; Liu J. Self-assembled nanostructures from C60-containing supramolecular complex: its stimuli-responsive reversible transition and biological antioxidative capacity, New J. Chem., 2011, 35, 2632-2638
  260. Akiyama, M.; Ikeda, A.; Shintani, T.; Doi, Y.; Kikuchi, J.; Ogawa, T.; Yogo, K.; Takeya, T.; Yamamoto, N. Solubilisation of [60]fullerenes using block copolymers and evaluation of their photodynamic activities, Org. Biomol. Chem., 2008, 6, 1015-1019
  261. Zhou, Z.; Lenk, R.P.; Dellinger, A.; Wilson, S.R.; Sadler, R.; Kepley, C.L. Liposomal formulation of amphiphilic fullerene antioxidants. Bioconj. Chem. 2010, 21, 1656–1661
  262. Chaudhuri, P.; Paraskar, A.; Soni, S.; Mashelkar, R.A.; Sengupta, S. Fullerenol-cytotoxic conjugates for cancer chemotherapy, ACS Nano, 2009, 3, 2505–2514
  263. Song, H.; Luo, S.; Wei, H.; Song, H.; Yang, Y.; Zhao, W. In vivo biological behavior of 99mTc(CO)3 labelled fullerol, J. Radioanal. Nucl. Chem., 2010, 285, 635-639
  264. Roberts, J.E.; Wielgus, A.R.; Boyes, W.K.; Andley, U.; Chignell, C.F. Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells, Toxicol. Appl. Pharmacol., 2008, 228, 49-58
  265. Zhao, B.; Yin, J.J.; Bilski, P.; Chignell, C.F.; Roberts, J.E.; He, Y.Y. Enhanced photodynamic efficacy towards melanoma cells by encapsulation of Pc4 in silica nanoparticles, Toxicol. Appl. Pharmacol., 2009, 241, 163–172
  266. Prow, T.W.; Bhutto, I.; Kim, S.Y.; Grebe, R.; Merges, C.; McLeod, D.S.; Uno, K.; Mennon, M.; Rodriguez, L.; Leong, K.; Lutty, G.A. Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium, Nanomedicine, 2008, 4, 340–349
  267. Bejjani, R.A.; BenEzra, D.; Cohen, H.; Rieger, J.; Andrieu, C.; Jeanny, J.C.; Gollomb, G.; Behar-Cohen, F.F. Nanoparticles for gene delivery to retinal pigment epithelial cells, Mol. Vis., 2005, 17, 124–132
  268. Yang, X.Y.; Edelmann, R.E.; Oris, J.T. Suspended C60 nanoparticles protect against short-term UV and fluoranthene photo-induced toxicity, but cause long-term cellular damage in Daphnia magna, Aquatic Toxicol., 2010, 100, 202-210
  269. Mroz, P.; Tegos, G.P.; Gali, H.; Wharton, T.; Sarna, T.; Hamblin, M.R. Photodynamic therapy with fullerenes, Photochem. Photobiol. Sci., 2007, 6, 1139–1149
  270. Burlaka, A.P.; Sidorik, U.P.; Prylutska, S.V. Catalytic system of the reactive oxygen species on the C60 fullerene basis, Exp. Oncol., 2004, 26, 326-327
  271. Meshalkin, Y.P.; Bgatova, N.P. Prospects and problems of the use of inorganics nanoparticles in oncology, J. Siber. Fed. Univ. B. (Russ.) 2008, 3, 248-268
  272. Mroz, P.; Pawlak, A.; Satti, M. Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism, Free Radical Biol. Med., 2007, 43, 711-719
  273. Yano, S.; Hirohara, S.; Obata, M.; Hagiya, Y.; Ogura, S.; Ikeda, A.; Kataoka, H.; Tanaka, M.; Joh, T. . Current states and future views in photodynamic therapy, J. Photochem. Photobiol. C, 2011, 12, 46– 67
  274. Hu, Z.; Zhang, C.; Huang, Y.; Sun, S.; Guan, W.; Yao Y. Photodynamic anticancer activities of water-soluble C60 derivatives and their biological consequences in a HeLa cell line, Chem.-Biol. Inter., 2012, 195, 86-94
  275. Ion, R.M.; Fierascu, R.C.; Neagu, M.; Constantin, C.; Stavaru, C. Porphyrin (TPP)–polyvinylpyrrolidone (PVP)–fullerene (C60) triad as novel sensitizer in photodynamic therapy, Sci. Adv. Mater., 2010, 2, 223-229
  276. Liao, F.; Saitoh, Y.; Miwa, N. Anticancer effects of fullerene [C60] included in polyethylene glycol combined with visible light irradiation through ROS generation and DNA fragmentation on fibrosarcoma cells with scarce cytotoxicity to normal fibroblasts, Oncol. Res. Feat. Preclin. Clin. Cancer Therap., 2011, 19, 203-216
  277. Liu, J.; Ohta, S.; Sonoda, A. Preparation of PEG-conjugated fullerene containing Gd3+ ions for photodynamic therapy, J. Controlled Release, 2007, 117, 104-110
  278. Jiang, G.; Li, G. Preparation, characterization, and properties of fullerene–vinylpyrrolidone copolymers, Biotechnol. Prog., 2012, 28, 215-222
  279. Vileno, B.; Jeney, S.; Sienkiewicz, A.; Marcoux, P.R.; Miller, L.M.; Forró, L. Evidence of lipid peroxidation and protein phosphorylation in cells upon oxidative stress photo-generated by fullerols, Biophys. Chem., 2010, 152, 164-169
  280. Badireddy, A.R.; Hotze, E.M.; Chellam, S.; Alvarez, P.; Wiesner, M.R. Inactivation of bacteriophages via photosensitization of fullerol nanoparticles, Environ. Sci. Technol., 2007, 41, 6627-6632
  281. Taroni, P.; D’Andrea, C.; Valentini, G.; Cubeddu, R.; Hu, D.N.; Roberts, J.E. Fullerol in human lens and retinal pigment epithelial cells: time domain fluorescence spectroscopy and imaging, Photochem. Photobiol. Sci., 2011, 10, 904–910
  282. Vileno, B.; Marcoux, P.R.; Lekka, M.; Sienkiewicz, A.; Feher, T.; Forró, L. Spectroscopic and photophysical properties of a highly derivatized C60 fullerol, Adv. Funct. Mater., 2006, 16, 120-128
  283. Sienkiewicz, A.; Vileno, B.; Pierzchała, K.; Czuba, M.; Marcoux, P.R.; Graczyk, A.; Fajer, P.G.; Forró, L. . Oxidative stress-mediated protein conformation changes: ESR study of spin-labelled staphylococcal nuclease, J. Phys. Condens. Matter, 2007, 19, 285201
  284. Straface, E.; Santini, M.T.; Donelli, G.; Giacomoni, P.U.; Malorni, W. Vitamin E prevents UVB-induced cell blebbing and cell death in A431 epidermoid cells, Int. J. Rad. Biol., 1995, 68, 579-587
  285. Ito, S.; Itoga, K.; Yamato, M.; Akamatsu, H.; Okano, T. The co-application effects of fullerene and ascorbic acid on UV-B irradiated mouse skin, Toxicology, 2010, 267, 27-38
  286. Kato, S.; Kikuchi, R.; Aoshima, H.; Saitoh, Y.; Miwa, N. Defensive effects of fullerene-C60/liposome complex against UVA-induced intracellular reactive oxygen species generation and cell death in human skin keratinocytes HaCaT, associated with intracellular uptake and extracellular excretion of fullerene-C60, J. Photochem. Photobiol. B., 2010, 98, 144-151
  287. Kato, S.; Aoshima, H.; Saitoh, Y.; Miwa, N. Fullerene-C60/liposome complex: Defensive effects against UVA-induced damages in skin structure, nucleus and collagen type I/IV fibrils, and the permeability into human skin tissue, J. Photochem. Photobiol. B, 2010, 98, 99-105
  288. Fumelli, C.; Marconi, A.; Salvioli, S.; Straface, E.; Malorni, W.; Offidani, A.M.; Pellicciari, R.; Schettini, G.; Giannetti, A.; Monti, D.; Franceschi, C.; Pincelli, C. Carboxyfullerenes protect human keratinocytes from ultraviolet-B-induced apoptosis, J. Invest. Dermatol., 2000, 115, 835–841
  289. Kato, S.; Ajshima, H.; Saitoh, Y.; Miwa, N. Fullerene-C60 Incorporated in Liposome Exerts Persistent Hydroxyl Radical-Scavenging Activity and Cytoprotection in UVA/B-Irradiated Keratinocytes, J. Nanosci. Nanotechnol., 2011, 11, 3814-3823
  290. Saitoh, Y.; Miyanishi, A.; Mizuno, H.; Kato, S.; Aoshima, H.; Kokubo, K.; Miwa, N. Super-highly hydroxylated fullerene derivative protects human keratinocytes from UV-induced cell injuries together with the decreases in intracellular ROS generation and DNA damages (2011), J. Photochem. Photobiol. B, 2011, 102, 69-76
  291. Zhao, B.; He, Y.Y.; Chignell, C.F.; Yin, J.J.; Andley, U.; Roberts, J.E. Difference in phototoxicity of cyclodextrin complexed fullerene [(γ-CyD)2/C60] and its aggregated derivatives toward human lens epithelial cells, Chem. Res. Toxicol., 2009, 22, 660-667
  292. Doi, Y.; Ikeda, A.; Akiyama, M.; Nagano, M.; Shigematsu, T.; Ogawa, T.; Takeya, T.; Nagasaki, T. Intracellular uptake and photodynamic activity of water-soluble [60]- and [70]fullerenes incorporated in liposomes, Chemistry: Eur. J., 2008, 14, 8892-8897
  293. Rancan, F.; Helmreich, M.; Mölich, A.; Jux, N.; Hirsch, A.; Röder, B.; Böhm, F. Intracellular Uptake and Phototoxicity of 31,32-Didehydrophytochlorin-fullerene Hexaadducts, Photochem. Photobiology, 2007, 83, 1330-1338
  294. Alvarez, M.; Prucca, C.; Milanesio, M.E.; Durantini, E.N.; Rivarola, V. Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its biological consequences in a human carcinoma cell line, Int. J. Biochem. Cell Biol., 2006, 38, 2092–2101
  295. Mikata, Y.; Takagi, S.; Tanahashi, M.; Ishii, S.; Obata, M.; Miyamoto, Y.; Wakita, K.; Nishisaka, T.; Hirano, T.; Ito, T.; Hoshino, M.; Ohtsuki, C.; Tanihara, M.; Yano, S. Detection of 1270 nm emission from singlet oxygen and photocytotoxic property of sugar-pendant [60] fullerenes, Bioorg. Med. Chem. Lett., 2003, 13, 3289–3292
  296. Otake, E.; Sakuma, S.; Torii, K.; Maeda, A.; Ohi, H.; Yano, S.; Morita, A. Effect and mechanism of a new photodynamic therapy with glycoconjugated fullerene, Photochem. Photobiol., 2010, 86, 1356–1363
  297. Horie, M.; Fukuhara, A.; Saito, Y.; Yoshida, Y.; Sato, H.; Ohi, H.; Obata, M.; Mikata, Y.; Yano, S.; Niki, E. Antioxidant action of sugar-pendant C60 fullerenes, Bioorg. Med. Chem. Lett., 2009, 19, 5902–5904
  298. Lebedev, V.T.; Torok, G.; Melenevskaya, E.Y.; Vinogradova, L.V.; Ivanova, I.N. Poly(N‐vinylcaprolactam)‐C60 complexes in aqueous solution, Fullerenes Nanotubes & Carbon Nanostructures, 2008, 16, 603-609
  299. Qiao, X.; Huang, C.; Ying, Y.; Yang, X.; Liu, Y.; Tian, Q. Involvement of reactive oxygen species and calcium in photo-induced membrane damage in HeLa cells by a bis-methanophosphonate fullerene, J. Photochem. Photobiol. B:, 2010, 98, 193–198
  300. Palyvoda, K.O.; Grynyuk, I.I.; Prylutsk, S.V.; Samoylenko, A.A.; Drobo, L.B.; Matyshevsk, O.P. Apoptosis photoinduction by C60 fullerene in human leukemic T cells, Ukr. Biochem. J., 2010, 82, 121-127
  301. Mroz, P.; Xia, Y.; Asanuma, D.; Konopko, A.; Zhiyentayev, T.; Huang, Y.Y.; Sharma, S.K.; Dai, T.; Khan, U.J.; Wharton, T.; Hamblin M.R. Intraperitoneal photodynamic therapy mediated by a fullerene in a mouse model of abdominal dissemination of colon adenocarcinoma, Nanomed.: Nanomed. Biol. Med., 2011, 7(6), 965-974
  302. Xiao, L.; Aoshima, H.; Saitoh, Y.; Miwa, N. Fullerene–polyvinylpyrrolidone clathrate localizes in the cytoplasm to prevent ultraviolet-A ray-induced DNA-fragmentation and activation of the transcriptional factor NF-kappaB, J. Cell. Biochem., 2010, 111, 955-966
  303. Constantin, C., Neagu, M.; Ion, R.; Gherghiceanu, M.; Stavaru, C. Fullerene-porphyrin nanostructures in photodynamic therapy, Nanomedicine, 2010, 5, 307-317
  304. Sharma, S.K.; Chiang, L.Y.; Hamblin, M.R. Photodenamic therapy with fullerenes in vivo: reality or a dream?, Nanomedicine, 2011, 6, 1813-1825
  305. Ni, J.; Q.Y.Wu, Y.G.Li, Z.X.Guo, G.S.Tang, D.Sun, F.Gao, J.M.Cai, Cytotoxic and radiosensitizing effects of nano-C60 on tumor cells in vitro, J. Nanoparticle Res., 2008, 10, 643-651
  306. Andrievsky, G.; Bruskov, V.I.; Tykhomyrov, A.A.; Gudkov, S.V. Peculiarities of the antioxidant and radioprotective effects of hydrated C60 fullerene nanostuctures in vitro and in vivo, Free Radic. Biol. Med., 2009, 47, 786-793
  307. Huang, S.Q.; Gao, Y.; Li, F.; Cui, B.; Zhao, J.; Dong, F.; Cai, J. Synthesis of fullerene derivative C(60)-Lys and its radio-protection effects in AHH-1 cell, J. Rad. Res. Rad. Proces., 2010, #1, 37-41
  308. Theriot, A.C.; Casey, R.C.; Moore, V.C.; Mitchell, L.; Reynolds, J.O.; Burgoyne, M.; Partha, R.; Huff, J.L.; Conyers, J.L.; Jeevarajan, A. Dendro[C60]fullerene DF-1 provides radioprotection to radiosensitive mammalian cells, Rad. Envir. Biophys., 2010, 49, 437-445
  309. Brown, A.P.; Chung, E.J.; Urick, M.E.; Shield, W.P.; Sowers, A.L.; Thetford, A.; Shankavaram, U.T.; Mitchell, J.V.; Citrin, D.E. Evaluation of the fullerene compound DF-1 as a radiation protector, Radiat. Oncol., 2010, 5, 34-43
  310. Daroczi, B.; Kari, G.; McAleer, M.F.; Wolf, J.C.; Rodeck, U.; Dicker, A.P. In vivo radioprotection by the fullerene nanoparticle DF-1as assessed in a Zebrafish model, Clin. Cancer Res., 2006, 12, 7086-7091
  311. Foley, S.; Crowley, C.; Smaihi, M.; Bonfils, C.; Erlanger, B.F.; Seta, P.; Larroque, C. Cellular localisation of a water-soluble fullerene derivative, Biochem. Biophys. Res. Commun., 2002, 294, 116–119
  312. Chirico, F.; Fumelli, C.; Marconi, A.; Tinari, A.; Straface, E.; Malorni, W.; Pellicciari, R.; Pincelli, C. Carboxyfullerenes localize within mitochondria and prevent the UVB-induced intrinsic apoptotic pathway, Exp. Dermatol., 2007, 16, 429–436
  313. Dobrovolskaia, M.A.; McNeil, S.E. Immunological properties of engineered nanomaterials, Nat. Nanotechnol., 2007, 2, 469–478
  314. Cai, X.; Hao, J.; Zhang, X.; Yu, B.; Ren, J.; Luo, C.; Li, Q.; Huang, Q.; Shi, X.; Li, W.; Liu, J. The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction, Toxicol. Appl. Pharmacol., 2010, 243, 27-34
  315. Injac, R.; Perse, M.; Cerne, M.; Potocnik, N.; Radic, N.; Govedarica, B.; Djordjevic, A.; Cerar, A.; Strukelj, B. Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer, Biomaterials, 2009, 30, 1184–1196
  316. Dordević, A.; Bogdanović, G., Fullerenol—a new nanopharmaceutic? Arch. Oncol., 2008, 16, 42–45
  317. Takada, H.; Kokubo, K.; Matsubayashi, K.; Oshima, T. Antioxidant activity of supramolecular water-soluble fullerenes evaluated by β-carotene bleaching assay, Biosci. Biotechnol. Biochem., 2006, 70, 3088-3093
  318. Vávrová, J.; Řezáčová, M.; Pejchal, J. Fullerene nanoparticles and their anti-oxidative effects: a comparison to other radioprotective agents, J. Appl. Biomed., 2012, 10, 1-8
  319. Fourches, D.; Pu, D.; Tassa, C.; Weissleder, R.; Shaw, S.Y.; Mumper, R.J.; Tropsha, A. Quantitative nanostructure-activity relationship modeling, AcsNano, 2010, 4, 5703-5712
  320. Kayat, J.; Gajbhiye, V.; Tekade, R.K.; Jain, N.K. Pulmonary toxicity of carbon nanotubes: a systematic report, Nanomed. Nanotechnol. Biol. Med., 2011, 7, 40-49
  321. Miller, J.; Lam, M.; Lebovitz, R. Derivatized Fullerenes: A New Class of Therapeutics and Imaging Agents. Nanotech. L. & Bus. http://heinonline.org/, 423, 2007
  322. Kepley, C. Use of fullerenes for the treatment of mast cell and basophil-mediated disease, US Patent 7947262, 2006
  323. Bystrzejewska-Piotrowska, G.; Golimowski, J.; Urban, P.L. Nanoparticles: Their potential toxicity, waste and environmental management, Waste Management, 2009, 29, 2587-2595
  324. Mraz, S.J. Nanowaste: the next big threat? Machine Design, 2005, 77, 46–53
  325. Lewinski, N.; Colvin, V.; Drezek, R. Cytotoxicity of nanoparticles, Small, 2008, 4, 26–49

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Volume 8, May 2019


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