Skip to main content
SpringerLink
Log in

Scavenging of reactive oxygen and nitrogen species with nanomaterials

  • Review Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Reactive oxygen and nitrogen species (RONS) are essential for normal physiological processes and play important roles in cell signaling, immunity, and tissue homeostasis. However, excess radical species are implicated in the development and augmented pathogenesis of various diseases. Several antioxidants may restore the chemical balance, but their use is limited by disappointing results of clinical trials. Nanoparticles are an attractive therapeutic alternative because they can change the biodistribution profile of antioxidants, and possess intrinsic ability to scavenge RONS. Herein, we review the types of RONS, how they are implicated in several diseases, and the types of nanoparticles with inherent antioxidant capability, their mechanisms of action, and their biological applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Commoner, B.; Townsend, J.; Pake, G. E. Free radicals in biological materials. Nature 1954, 174, 689–691.

    Google Scholar 

  2. Alfadda, A. A.; Sallam, R. M. Reactive oxygen species in health and disease. J. Biomed. Biotechnol. 2012, 2012, 936486.

    Google Scholar 

  3. Bayir, H. Reactive oxygen species. Crit. Care Med. 2005, 33, S498–S501.

    Google Scholar 

  4. Dhawan, V. Reactive oxygen and nitrogen species: General considerations. In Studies on Respiratory Disorders; Ganguly, N. K.; Jindal, S. K.; Biswal, S.; Barnes, P. J.; Pawankar, R., Eds.; Humana Press: New York, 2014; pp 27–47.

    Google Scholar 

  5. McCord, J. M.; Fridovich, I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 1969, 244, 6049–6055.

    Google Scholar 

  6. Rhee, S. G.; Woo, H. A.; Kil, I. S.; Bae, S. H. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J. Biol. Chem. 2012, 287, 4403–4410.

    Google Scholar 

  7. Ray, P. D.; Huang, B. W.; Tsuji, Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell. Signal. 2012, 24, 981–990.

    Google Scholar 

  8. Olmez, I.; Ozyurt, H. Reactive oxygen species and ischemic cerebrovascular disease. Neurochem. Int. 2012, 60, 208–212.

    Google Scholar 

  9. Galley, H. F. Oxidative stress and mitochondrial dysfunction in sepsis. Br. J. Anaesth. 2011, 107, 57–64.

    Google Scholar 

  10. Urakawa, H.; Katsuki, A.; Sumida, Y.; Gabazza, E. C.; Murashima, S.; Morioka, K.; Maruyama, N.; Kitagawa, N.; Tanaka, T.; Hori, Y. et al. Oxidative stress is associated with adiposity and insulin resistance in men. J. Clin. Endocrinol. Metab. 2003, 88, 4673–4676.

    Google Scholar 

  11. Datla, S. R.; Griendling, K. K. Reactive oxygen species, NADPH oxidases, and hypertension. Hypertension 2010, 56, 325–330.

    Google Scholar 

  12. Kim, G. H.; Kim, J. E.; Rhie, S. J.; Yoon, S. The role of oxidative stress in neurodegenerative diseases. Exp. Neurobiol. 2015, 24, 325–340.

    Google Scholar 

  13. Salminen, A.; Ojala, J.; Kaarniranta, K.; Kauppinen, A. Mitochondrial dysfunction and oxidative stress activate inflammasomes: Impact on the aging process and age–related diseases. Cell. Mol. Life Sci. 2012, 69, 2999–3013.

    Google Scholar 

  14. Liou, G. Y.; Storz, P. Reactive oxygen species in cancer. Free Radic. Res. 2010, 44, 479–496.

    Google Scholar 

  15. Hahn, S. M.; Lepinski, D. L.; DeLuca, A. M.; Mitchell, J. B.; Pellmar, T. C. Neurophysiological consequences of nitroxide antioxidants. Can. J. Physiol. Pharmacol. 1995, 73, 399–403.

    Google Scholar 

  16. Samuni, A.; Krishna, C. M.; Riesz, P.; Finkelstein, E.; Russo, A. A novel metal–free low molecular weight superoxide dismutase mimic. J. Biol. Chem. 1988, 263, 17921–17924.

    Google Scholar 

  17. Firuzi, O.; Miri, R.; Tavakkoli, M.; Saso, L. Antioxidant therapy: Current status and future prospects. Curr. Med. Chem. 2011, 18, 3871–3888.

    Google Scholar 

  18. Iannitti, T.; Palmieri, B. Antioxidant therapy effectiveness: An up to date. Eur. Rev. Med. Pharmacol. Sci. 2009, 13, 245–278.

    Google Scholar 

  19. Bjelakovic, G.; Nikolova, D.; Simonetti, R. G.; Gluud, C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst. Rev. 2008, DOI: 10.1002/14651858.CD004183.pub3.

    Google Scholar 

  20. Lirussi, F.; Azzalini, L.; Orando, S.; Orlando, R.; Angelico, F. Antioxidant supplements for non–alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst. Rev. 2007, DOI: 10.1002/14651858.CD004996.pub3.

    Google Scholar 

  21. Orrell, R. W.; Lane, R. J.; Ross, M. A systematic review of antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. Amyotroph. Lateral Scler. 2008, 9, 195–211.

    Google Scholar 

  22. Farinotti, M.; Vacchi, L.; Simi, S.; Di Pietrantonj, C.; Brait, L.; Filippini, G. Dietary interventions for multiple sclerosis. Cochrane Database Syst. Rev. 2012, DOI: 10.1002/14651858.CD004192.pub3.

    Google Scholar 

  23. Shaheen, S. O.; Newson, R. B.; Rayman, M. P.; Wong, A. P. L.; Tumilty, M. K.; Phillips, J. M.; Potts, J. F.; Kelly, F. J.; White, P. T.; Burney, P. G. J. Randomised, double blind, placebo–controlled trial of selenium supplementation in adult asthma. Thorax 2007, 62, 483–490.

    Google Scholar 

  24. Cochemé, H. M.; Murphy, M. P. Can antioxidants be effective therapeutics? Curr. Opin. Invest. Drugs 2010, 11, 426–431.

    Google Scholar 

  25. Marchioli, R.; Schweiger, C.; Levantesi, G.; Tavazzi, L.; Valagussa, F. Antioxidant vitamins and prevention of cardiovascular disease: Epidemiological and clinical trial data. Lipids 2001, 36, S53–S63.

    Google Scholar 

  26. Chonpathompikunlert, P.; Fan, C. H.; Ozaki, Y.; Yoshitomi, T.; Yeh, C. K.; Nagasaki, Y. Redox nanoparticle treatment protects against neurological deficit in focused ultrasoundinduced intracerebral hemorrhage. Nanomedicine 2012, 7, 1029–1043.

    Google Scholar 

  27. Nash, K. M.; Ahmed, S. Nanomedicine in the ROS–mediated pathophysiology: Applications and clinical advances. Nanomedicine 2015, 11, 2033–2040.

    Google Scholar 

  28. Ozcan, A.; Ogun, M. Biochemistry of reactive oxygen and nitrogen species. In Basic Principles and Clinical Significance of Oxidative Stress; InTech: Rijeka, 2015.

    Google Scholar 

  29. Murphy, M. P. How mitochondria produce reactive oxygen species. Biochem. J. 2009, 417, 1–13.

    Google Scholar 

  30. Fridovich, I. Superoxide dismutases. An adaptation to a paramagnetic gas. J. Biol. Chem. 1989, 264, 7761–7764.

    Google Scholar 

  31. Fukuzawa, K.; Gebicki, J. M. Oxidation of α–tocopherol in micelles and liposomes by the hydroxyl, perhydroxyl, and superoxide free radicals. Arch. Biochem. Biophys. 1983, 226, 242–251.

    Google Scholar 

  32. Sheng, Y. W.; Abreu, I. A.; Cabelli, D. E.; Maroney, M. J.; Miller, A. F.; Teixeira, M.; Valentine, J. S. Superoxide dismutases and superoxide reductases. Chem. Rev. 2014, 114, 3854–3918.

    Google Scholar 

  33. Winterbourn, C. C. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 2008, 4, 278–286.

    Google Scholar 

  34. Rhee, S. G.; Yang, K. S.; Kang, S. W.; Woo, H. A.; Chang, T. S. Controlled elimination of intracellular H2O2: Regulation of peroxiredoxin, catalase, and glutathione peroxidase via post–translational modification. Antioxid. Redox Signal. 2005, 7, 619–626.

    Google Scholar 

  35. Pastor, N.; Weinstein, H.; Jamison, E.; Brenowitz, M. A detailed interpretation of OH radical footprints in a TBP–DNA complex reveals the role of dynamics in the mechanism of sequence–specific binding. J. Mol. Biol. 2000, 304, 55–68.

    Google Scholar 

  36. Halliwell, B. Oxidants and human–disease: Some new concepts. FASEB J. 1987, 1, 358–364.

    Google Scholar 

  37. Kehrer, J. P. The Haber–Weiss reaction and mechanisms of toxicity. Toxicology 2000, 149, 43–50.

    Google Scholar 

  38. Buonocore, G.; Perrone, S.; Tataranno, M. L. Oxygen toxicity: Chemistry and biology of reactive oxygen species. Semin. Fetal Neonatal Med. 2010, 15, 186–190.

    Google Scholar 

  39. Augusto, O.; Miyamoto, S. Oxygen radicals and related species. In Principles of Free Radical Biomedicine; Pantopoulos, K.; Schipper, H. M., Eds.; Nova Science Publishers, Inc., 2011; pp 1–23.

    Google Scholar 

  40. Nathan, C.; Xie, Q. W. Regulation of biosynthesis of nitric oxide. J. Biol. Chem. 1994, 269, 13725–13728.

    Google Scholar 

  41. Martínez, M. C.; Andriantsitohaina, R. Reactive nitrogen species: Molecular mechanisms and potential significance in health and disease. Antioxid. Redox Signal. 2009, 11, 669–702.

    Google Scholar 

  42. Patel, R. P.; McAndrew, J.; Sellak, H.; White, C. R.; Jo, H.; Freeman, B. A.; Darley–Usmar, V. M. Biological aspects of reactive nitrogen species. Biochim. Biophys. Acta 1999, 1411, 385–400.

    Google Scholar 

  43. De Grey, A. D. J. HO2 •: The forgotten radical. DNA Cell Biol. 2002, 21, 251–257.

    Google Scholar 

  44. Pullar, J. M.; Vissers, M. C. M.; Winterbourn, C. C. Living with a killer: The effects of hypochlorous acid on mammalian cells. IUBMB Life 2000, 50, 259–266.

    Google Scholar 

  45. Lee, J.; Koo, N.; Min, D. B. Reactive oxygen species, aging, and antioxidative nutraceuticals. Compr. Rev. Food Sci. F. 2004, 3, 21–33.

    Google Scholar 

  46. Bartosz, G. Reactive oxygen species: Destroyers or messengers? Biochem. Pharmacol. 2009, 77, 1303–1315.

    Google Scholar 

  47. Sharma, P.; Jha, A. B.; Dubey, R. S.; Pessarakli, M. Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. J. Bot. 2012, 2012, Article ID 217037.

    Google Scholar 

  48. Birben, E.; Sahiner, U. M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J. 2012, 5, 9–19.

    Google Scholar 

  49. Dizdaroglu, M.; Jaruga, P.; Birincioglu, M.; Rodriguez, H. Free radical–induced damage to DNA: Mechanisms and measurement. Free Radic. Biol. Med. 2002, 32, 1102–1115.

    Google Scholar 

  50. Phaniendra, A.; Jestadi, D. B.; Periyasamy, L. Free radicals: Properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem. 2015, 30, 11–26.

    Google Scholar 

  51. Dean, R. T.; Fu, S.; Stocker, R.; Davies, M. J. Biochemistry and pathology of radical–mediated protein oxidation. Biochem. J. 1997, 324, 1–18.

    Google Scholar 

  52. Butterfield, D. A.; Koppal, T.; Howard, B.; Subramaniam, R.; Hall, N.; Hensley, K.; Yatin, S.; Allen, K.; Aksenov, M.; Aksenova, M. et al. Structural and functional changes in proteins induced by free radical–mediated oxidative stress and protective action of the antioxidants N–tert–butyl–α–phenylnitrone and vitamin Ea. Ann. N Y Acad. Sci. 1998, 854, 448–462.

    Google Scholar 

  53. Chevion, M.; Berenshtein, E.; Stadtman, E. R. Human studies related to protein oxidation: Protein carbonyl content as a marker of damage. Free Radical Res. 2000, 33, S99–S108.

    Google Scholar 

  54. Shimizu, M.; Yoshitomi, T.; Nagasaki, Y. The behavior of ROS–scavenging nanoparticles in blood. J. Clin. Biochem. Nutr. 2014, 54, 166–173.

    Google Scholar 

  55. Yoshitomi, T.; Hirayama, A.; Nagasaki, Y. The ROS scavenging and renal protective effects of pH–responsive nitroxide radical–containing nanoparticles. Biomaterials 2011, 32, 8021–8028.

    Google Scholar 

  56. Nagasaki, Y. Nitroxide radicals and nanoparticles: A partnership for nanomedicine radical delivery. Ther. Deliv. 2012, 3, 165–179.

    Google Scholar 

  57. Vong, L. B.; Kobayashi, M.; Nagasaki, Y. Evaluation of the toxicity and antioxidant activity of redox nanoparticles in zebrafish (Danio rerio) embryos. Mol. Pharm. 2016, 13, 3091–3097.

    Google Scholar 

  58. Yue, C. X.; Yang, Y. M.; Zhang, C. L.; Alfranca, G.; Cheng, S. L.; Ma, L. J.; Liu, Y. L.; Zhi, X.; Ni, J.; Jiang, W. H. et al. ROS–responsive mitochondria–targeting blended nanoparticles: Chemo–and photodynamic synergistic therapy for lung cancer with on–demand drug release upon irradiation with a single light source. Theranostics 2016, 6, 2352–2366.

    Google Scholar 

  59. Yoshitomi, T.; Nagasaki, Y. Nitroxyl radical–containing nanoparticles for novel nanomedicine against oxidative stress injury. Nanomedicine 2011, 6, 509–518.

    Google Scholar 

  60. Vong, L. B.; Tomita, T.; Yoshitomi, T.; Matsui, H.; Nagasaki, Y. An orally administered redox nanoparticle that accumulates in the colonic mucosa and reduces colitis in mice. Gastroenterology 2012, 143, 1027–1036.

    Google Scholar 

  61. Marushima, A.; Suzuki, K.; Nagasaki, Y.; Yoshitomi, T.; Toh, K.; Tsurushima, H.; Hirayama, A.; Matsumura, A. Newly synthesized radical–containing nanoparticles enhance neuroprotection after cerebral ischemia–reperfusion injury. Neurosurgery 2011, 68, 1418–1426.

    Google Scholar 

  62. Kalmodia, S.; Vandhana, S.; Tejaswini Rama, B. R.; Jayashree, B.; Sreenivasan Seethalakshmi, T.; Umashankar, V.; Yang, W. R.; Barrow, C. J.; Krishnakumar, S.; Elchuri, S. V. Bioconjugation of antioxidant peptide on surface–modified gold nanoparticles: A novel approach to enhance the radical scavenging property in cancer cell. Cancer Nanotechnol. 2016, 7, 1.

    Google Scholar 

  63. Li, J. C.; Zhang, J.; Chen, Y.; Kawazoe, N.; Chen, G. P. TEMPO–conjugated gold nanoparticles for reactive oxygen species scavenging and regulation of stem cell differentiation. ACS Appl. Mater. Interfaces 2017, 9, 35683–35692.

    Google Scholar 

  64. Pu, H. L.; Chiang, W. L.; Maiti, B.; Liao, Z. X.; Ho, Y. C.; Shim, M. S.; Chuang, E. Y.; Xia, Y. N.; Sung, H. W. Nanoparticles with dual responses to oxidative stress and reduced pH for drug release and anti–inflammatory applications. ACS Nano 2014, 8, 1213–1221.

    Google Scholar 

  65. Celardo, I.; Pedersen, J. Z.; Traversa, E.; Ghibelli, L. Pharmacological potential of cerium oxide nanoparticles. Nanoscale 2011, 3, 1411–1420.

    Google Scholar 

  66. Korsvik, C.; Patil, S.; Seal, S.; Self, W. T. Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem. Commun. 2007, 1056–1058.

    Google Scholar 

  67. Singh, S.; Dosani, T.; Karakoti, A. S.; Kumar, A.; Seal, S.; Self, W. T. A phosphate–dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials 2011, 32, 6745–6753.

    Google Scholar 

  68. Lee, S. S.; Song, W. S.; Cho, M.; Puppala, H. L.; Nguyen, P.; Zhu, H. G.; Segatori, L.; Colvin, V. L. Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating. ACS Nano 2013, 7, 9693–9703.

    Google Scholar 

  69. Pirmohamed, T.; Dowding, J. M.; Singh, S.; Wasserman, B.; Heckert, E.; Karakoti, A. S.; King, J. E. S.; Seal, S.; Self, W. T. Nanoceria exhibit redox state–dependent catalase mimetic activity. Chem. Commun. 2010, 46, 2736–2738.

    Google Scholar 

  70. Migani, A.; Vayssilov, G. N.; Bromley, S. T.; Illas, F.; Neyman, K. M. Dramatic reduction of the oxygen vacancy formation energy in ceria particles: A possible key to their remarkable reactivity at the nanoscale. J. Mater. Chem. 2010, 20, 10535–10546.

    Google Scholar 

  71. Das, M.; Patil, S.; Bhargava, N.; Kang, J. F.; Riedel, L. M.; Seal, S.; Hickman, J. J. Auto–catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 2007, 28, 1918–1925.

    Google Scholar 

  72. Perez, J. M.; Asati, A.; Nath, S.; Kaittanis, C. Synthesis of biocompatible dextran–coated nanoceria with pH–dependent antioxidant properties. Small 2008, 4, 552–556.

    Google Scholar 

  73. Niu, J. L.; Azfer, A.; Rogers, L. M.; Wang, X. H.; Kolattukudy, P. E. Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc. Res. 2007, 73, 549–559.

    Google Scholar 

  74. Mandoli, C.; Pagliari, F.; Pagliari, S.; Forte, G.; Di Nardo, P.; Licoccia, S.; Traversa, E. Stem cell aligned growth induced by CeO2 nanoparticles in PLGA scaffolds with improved bioactivity for regenerative medicine. Adv. Funct. Mater. 2010, 20, 1617–1624.

    Google Scholar 

  75. Hirst, S. M.; Karakoti, A. S.; Tyler, R. D.; Sriranganathan, N.; Seal, S.; Reilly, C. M. Anti–inflammatory properties of cerium oxide nanoparticles. Small 2009, 5, 2848–2856.

    Google Scholar 

  76. Karakoti, A.; Singh, S.; Dowding, J. M.; Seal, S.; Self, W. T. Redox–active radical scavenging nanomaterials. Chem. Soc. Rev. 2010, 39, 4422–4432.

    Google Scholar 

  77. Tsai, Y. Y.; Oca–Cossio, J.; Agering, K.; Simpson, N. E.; Atkinson, M. A.; Wasserfall, C. H.; Constantinidis, I.; Sigmund, W. Novel synthesis of cerium oxide nanoparticles for free radical scavenging. Nanomedicine 2007, 2, 325–332.

    Google Scholar 

  78. Chen, J. P.; Patil, S.; Seal, S.; McGinnis, J. F. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat. Nanotechnol. 2006, 1, 142–150.

    Google Scholar 

  79. Colon, J.; Herrera, L.; Smith, J.; Patil, S.; Komanski, C.; Kupelian, P.; Seal, S.; Jenkins, D. W.; Baker, C. H. Protection from radiation–induced pneumonitis using cerium oxide nanoparticles. Nanomedicine 2009, 5, 225–231.

    Google Scholar 

  80. Kim, C. K.; Kim, T.; Choi, I. Y.; Soh, M.; Kim, D.; Kim, Y. J.; Jang, H.; Yang, H. S.; Kim, J. Y.; Park, H. K. et al. Ceria nanoparticles that can protect against ischemic stroke. Angew. Chem., Int. Ed. 2012, 51, 11039–11043.

    Google Scholar 

  81. Soh, M.; Kang, D. W.; Jeong, H. G.; Kim, D.; Kim, D. Y.; Yang, W.; Song, C.; Baik, S.; Choi, I. Y.; Ki, S. K. et al. Ceria–zirconia nanoparticles as an enhanced multi–antioxidant for sepsis treatment. Angew. Chem., Int. Ed. 2017, 56, 11399–11403.

    Google Scholar 

  82. Kang, D. W.; Kim, C. K.; Jeong, H. G.; Soh, M.; Kim, T.; Choi, I. Y.; Ki, S. K.; Kim, D. Y.; Yang, W.; Hyeon, T. et al. Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage. Nano Res. 2017, 10, 2743–2760.

    Google Scholar 

  83. Wu, H. B.; Li, F. Y.; Wang, S. F.; Lu, J. X.; Li, J. Q.; Du, Y.; Sun, X. L.; Chen, X. Y.; Gao, J. Q.; Ling, D. S. Ceria nanocrystals decorated mesoporous silica nanoparticle based ROS–scavenging tissue adhesive for highly efficient regenerative wound healing. Biomaterials 2018, 151, 66–77.

    Google Scholar 

  84. Fenoglio, I.; Tomatis, M.; Lison, D.; Muller, J.; Fonseca, A.; Nagy, J. B.; Fubini, B. Reactivity of carbon nanotubes: Free radical generation or scavenging activity? Free Radic. Biol. Med. 2006, 40, 1227–1233.

    Google Scholar 

  85. Krusic, P. J.; Wasserman, E.; Keizer, P. N.; Morton, J. R.; Preston, K. F. Radical reactions of C60. Science 1991, 254, 1183–1185.

    Google Scholar 

  86. Morton, J. R.; Preston, K. F.; Krusic, P. J.; Hill, S. A.; Wasserman, E. ESR studies of the reaction of alkyl radicals with fullerene C60. J. Phys. Chem. 1992, 96, 3576–3578.

    Google Scholar 

  87. Lin, A. M. Y.; Chyi, B. Y.; Wang, S. D.; Yu, H. H.; Kanakamma, P. P.; Luh, T. Y.; Chou, C. K.; Ho, L. T. Carboxyfullerene prevents iron–induced oxidative stress in rat brain. J. Neurochem. 1999, 72, 1634–1640.

    Google Scholar 

  88. Ying, Y. M.; Saini, R. K.; Liang, F.; Sadana, A. K.; Billups, W. E. Functionalization of carbon nanotubes by free radicals. Org. Lett. 2003, 5, 1471–1473.

    Google Scholar 

  89. Galano, A. Carbon nanotubes as free–radical scavengers. J. Phys. Chem. C 2008, 112, 8922–8927.

    Google Scholar 

  90. Lucente–Schultz, R. M.; Moore, V. C.; Leonard, A. D.; Price, B. K.; Kosynkin, D. V.; Lu, M.; Partha, R.; Conyers, J. L.; Tour, J. M. Antioxidant single–walled carbon nanotubes. J. Am. Chem. Soc. 2009, 131, 3934–3941.

    Google Scholar 

  91. Huq, R.; Samuel, E. L. G.; Sikkema, W. K. A.; Nilewski, L. G.; Lee, T.; Tanner, M. R.; Khan, F. S.; Porter, P. C.; Tajhya, R. B.; Patel, R. S. et al. Preferential uptake of antioxidant carbon nanoparticles by T lymphocytes for immunomodulation. Sci. Rep. 2016, 6, 33808.

    Google Scholar 

  92. Lee, H. J.; Park, J.; Yoon, O. J.; Kim, H. W.; Lee, D. Y.; Kim, D. H.; Lee, W. B.; Lee, N. E.; Bonventre, J. V.; Kim, S. S. Amine–modified single–walled carbon nanotubes protect neurons from injury in a rat stroke model. Nat. Nanotechnol. 2011, 6, 121–125.

    Google Scholar 

  93. Yudoh, K.; Karasawa, R.; Masuko, K.; Kato, T. Watersoluble fullerene (C60) inhibits the development of arthritis in the rat model of arthritis. Int. J. Nanomedicine 2009, 4, 217–225.

    Google Scholar 

  94. Huang, S. T.; Ho, C. S.; Lin, C. M.; Fang, H. W.; Peng, Y. X. Development and biological evaluation of C60 fulleropyrrolidine–thalidomide dyad as a new anti–inflammation agent. Bioorg. Med. Chem. 2008, 16, 8619–8626.

    Google Scholar 

  95. Bitner, B. R.; Marcano, D. C.; Berlin, J. M.; Fabian, R. H.; Cherian, L.; Culver, J. C.; Dickinson, M. E.; Robertson, C. S.; Pautler, R. G.; Kent, T. A. et al. Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury. ACS Nano 2012, 6, 8007–8014.

    Google Scholar 

  96. Liu, X.; Wang, Q.; Zhao, H. H.; Zhang, L. C.; Su, Y. Y.; Lv, Y. BSA–templated MnO2 nanoparticles as both peroxidase and oxidase mimics. Analyst 2012, 137, 4552–4558.

    Google Scholar 

  97. Li, W.; Liu, Z.; Liu, C. Q.; Guan, Y. J.; Ren, J. S.; Qu, X. G. Manganese dioxide nanozymes as responsive cytoprotective shells for individual living cell encapsulation. Angew. Chem., Int. Ed. 2017, 56, 13661–13665.

    Google Scholar 

  98. Huang, Y. Y.; Liu, Z.; Liu, C. Q.; Ju, E. G.; Zhang, Y.; Ren, J. S.; Qu, X. G. Self–assembly of multi–nanozymes to mimic an intracellular antioxidant defense system. Angew. Chem., Int. Ed. 2016, 55, 6646–6650.

    Google Scholar 

  99. Wan, Y.; Qi, P.; Zhang, D.; Wu, J. J.; Wang, Y. Manganese oxide nanowire–mediated enzyme–linked immunosorbent assay. Biosens. Bioelectron. 2012, 33, 69–74.

    Google Scholar 

  100. Luo, X. L.; Xu, J. J.; Zhao, W.; Chen, H. Y. A novel glucose ENFET based on the special reactivity of MnO2 nanoparticles. Biosens. Biolectron. 2004, 19, 1295–1300.

    Google Scholar 

  101. Prasad, P.; Gordijo, C. R.; Abbasi, A. Z.; Maeda, A.; Ip, A.; Rauth, A. M.; DaCosta, R. S.; Wu, X. Y. Multifunctional albumin–MnO2 nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response. ACS Nano 2014, 8, 3202–3212.

    Google Scholar 

  102. Hikosaka, K.; Kim, J.; Kajita, M.; Kanayama, A.; Miyamoto, Y. Platinum nanoparticles have an activity similar to mitochondrial NADH: Ubiquinone oxidoreductase. Colloids Surf. B: Biointerfaces 2008, 66, 195–200.

    Google Scholar 

  103. Tabata, S.; Nishida, H.; Masaki, Y.; Tabata, K. Stoichiometric photocatalytic decomposition of pure water in Pt/TiO2 aqueous suspension system. Catal. Lett. 1995, 34, 245–249.

    Google Scholar 

  104. Watanabe, A.; Kajita, M.; Kim, J.; Kanayama, A.; Takahashi, K.; Mashino, T.; Miyamoto, Y. In vitro free radical scavenging activity of platinum nanoparticles. Nanotechnology 2009, 20, 455105.

    Google Scholar 

  105. Huang, B.; Zhang, J. S.; Hou, J. W.; Chen, C. Free radical scavenging efficiency of Nano–Se in vitro. Free Radic. Biol. Med. 2003, 35, 805–813.

    Google Scholar 

  106. Katsumi, H.; Fukui, K.; Sato, K.; Maruyama, S.; Yamashita, S.; Mizumoto, E.; Kusamori, K.; Oyama, M.; Sano, M.; Sakane, T. et al. Pharmacokinetics and preventive effects of platinum nanoparticles as reactive oxygen species scavengers on hepatic ischemia/reperfusion injury in mice. Metallomics 2014, 6, 1050–1056.

    Google Scholar 

  107. Ju, K. Y.; Lee, Y.; Lee, S.; Park, S. B.; Lee, J. K. Bioinspired polymerization of dopamine to generate melanin–like nanoparticles having an excellent free–radicalscavenging property. Biomacromolecules 2011, 12, 625–632.

    Google Scholar 

  108. Panzella, L.; Gentile, G.; D'Errico, G.; Della Vecchia, N. F.; Errico, M. E.; Napolitano, A.; Carfagna, C.; d'Ischia, M. Atypical structural and π–electron features of a melanin polymer that lead to superior free–radical–scavenging properties. Angew. Chem., Int. Ed. 2013, 52, 12684–12687.

    Google Scholar 

  109. Liu, Y. L.; Ai, K. L.; Ji, X. Y.; Askhatova, D.; Du, R.; Lu, L. H.; Shi, J. J. Comprehensive insights into the multiantioxidative mechanisms of melanin nanoparticles and their application to protect brain from injury in ischemic stroke. J. Am. Chem. Soc. 2017, 139, 856–862.

    Google Scholar 

  110. Tapiero, H.; Townsend, D. M.; Tew, K. D. The antioxidant role of selenium and seleno–compounds. Biomed. Pharmacother. 2003, 57, 134–144.

    Google Scholar 

  111. Qin, S. Y.; Huang, B. X.; Ma, J. F.; Wang, X.; Zhang, J. B.; Li, L. H.; Chen, F. Effects of selenium–chitosan on blood selenium concentration, antioxidation status, and cellular and humoral immunity in mice. Biol. Trace Elem. Res. 2015, 165, 145–152.

    Google Scholar 

  112. Zhai, X. N.; Zhang, C. Y.; Zhao, G. H.; Stoll, S.; Ren, F. Z.; Leng, X. J. Antioxidant capacities of the selenium nanoparticles stabilized by chitosan. J. Nanobiotechnology 2017, 15, 4.

    Google Scholar 

  113. Li, F.; Li, T. Y.; Sun, C. X.; Xia, J. H.; Jiao, Y.; Xu, H. P. Selenium–doped carbon quantum dots for free–radical scavenging. Angew. Chem., Int. Ed. 2017, 56, 9910–9914.

    Google Scholar 

  114. Chan, P. H. Role of oxidants in ischemic brain damage. Stroke 1996, 27, 1124–1129.

    Google Scholar 

  115. Alexandrova, M. L.; Bochev, P. G.; Markova, V. I.; Bechev, B. G.; Popova, M. A.; Danovska, M. P.; Simeonova, V. K. Oxidative stress in the chronic phase after stroke. Redox Rep. 2003, 8, 169–176.

    Google Scholar 

  116. Galley, H. F.; Davies, M. J.; Webster, N. R. Xanthine oxidase activity and free radical generation in patients with sepsis syndrome. Crit. Care Med. 1996, 24, 1649–1653.

    Google Scholar 

  117. Takeda, K.; Shimada, Y.; Amano, M.; Sakai, T.; Okada, T.; Yoshiya, I. Plasma lipid peroxides and alpha–tocopherol in critically ill patients. Crit. Care Med. 1984, 12, 957–959.

    Google Scholar 

  118. Borrelli, E.; Roux–Lombard, P.; Grau, G. E.; Girardin, E.; Ricou, B.; Dayer, J. M.; Suter, P. M. Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk. Crit. Care Med. 1996, 24, 392–397.

    Google Scholar 

  119. Victor, V. M.; Espulgues, J. V.; Hernández–Mijares, A.; Rocha, M. Oxidative stress and mitochondrial dysfunction in sepsis: A potential therapy with mitochondria–targeted antioxidants. Infect. Disord. Drug Targets 2009, 9, 376–389.

    Google Scholar 

  120. Levy, R. J.; Vijayasarathy, C.; Raj, N. R.; Avadhani, N. G.; Deutschman, C. S. Competitive and noncompetitive inhibition of myocardial cytochrome C oxidase in sepsis. Shock 2004, 21, 110–114.

    Google Scholar 

  121. Taylor, D. E.; Ghio, A. J.; Piantadosi, C. A. Reactive oxygen species produced by liver mitochondria of rats in sepsis. Arch. Biochem. Biophys. 1995, 316, 70–76.

    Google Scholar 

  122. Brealey, D.; Brand, M.; Hargreaves, I.; Heales, S.; Land, J.; Smolenski, R.; Davies, N. A.; Cooper, C. E.; Singer, M. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 2002, 360, 219–223.

    Google Scholar 

  123. Levy, R. J. Mitochondrial dysfunction, bioenergetic impairment, and metabolic down–regulation in sepsis. Shock 2007, 28, 24–28.

    Google Scholar 

  124. Berger, M. M.; Chioléro, R. L. Antioxidant supplementation in sepsis and systemic inflammatory response syndrome. Crit. Care Med. 2007, 35, S584–S590.

    Google Scholar 

  125. Manoharan, S.; Guillemin, G. J.; Abiramasundari, R. S.; Essa, M. M.; Akbar, M.; Akbar, M. D. The role of reactive oxygen species in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease: A mini review. Oxid. Med. Cell. Longev. 2016, 2016, Article ID 8590578.

    Google Scholar 

  126. Nakajima, K.; Kohsaka, S. Microglia: Activation and their significance in the central nervous system. J. Biochem. 2001, 130, 169–175.

    Google Scholar 

  127. Friedman, J. Why is the nervous system vulnerable to oxidative stress? In Oxidative Stress and Free Radical Damage in Neurology; Gadoth, N.; Göbel, H. H., Eds.; Humana Press: Totowa, NJ, 2011; pp 19–27.

  128. Blesa, J.; Trigo–Damas, I.; Quiroga–Varela, A.; Jackson–Lewis, V. R. Oxidative stress and Parkinson’s disease. Front. Neuroanat. 2015, 9, 91.

    Google Scholar 

  129. Gerlach, M.; Double, K. L.; Ben–Shachar, D.; Zecca, L.; Youdim, M. B. H.; Riederer, P. Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease. Neurotox. Res. 2003, 5, 35–43.

    Google Scholar 

  130. Ihara, Y.; Chuda, M.; Kuroda, S.; Hayabara, T. Hydroxyl radical and superoxide dismutase in blood of patients with Parkinson’s disease: Relationship to clinical data. J. Neurol. Sci. 1999, 170, 90–95.

    Google Scholar 

  131. Barber, S. C.; Mead, R. J.; Shaw, P. J. Oxidative stress in ALS: A mechanism of neurodegeneration and a therapeutic target. Biochim. Biophys. Acta 2006, 1762, 1051–1067.

    Google Scholar 

  132. Said Ahmed, M.; Hung, W. Y.; Zu, J. S.; Hockberger, P.; Siddique, T. Increased reactive oxygen species in familial amyotrophic lateral sclerosis with mutations in SOD1. J. Neurol. Sci. 2000, 176, 88–94.

    Google Scholar 

  133. Kumar, A.; Ratan, R. R. Oxidative stress and Huntington’s disease: The good, the bad, and the ugly. J. Huntingtons Dis. 2016, 5, 217–237.

    Google Scholar 

  134. Gil–Mohapel, J.; Brocardo, P. S.; Christie, B. R. The role of oxidative stress in Huntington’s disease: Are antioxidants good therapeutic candidates? Curr. Drug Targets 2014, 15, 454–468.

    Google Scholar 

  135. Kwon, H. J.; Cha, M. Y.; Kim, D.; Kim, D. K.; Soh, M.; Shin, K.; Hyeon, T.; Mook–Jung, I. Mitochondria–targeting ceria nanoparticles as antioxidants for Alzheimer’s disease. ACS Nano 2016, 10, 2860–2870.

    Google Scholar 

  136. Blair, M. Diabetes mellitus review. Urol. Nurs. 2016, 36, 27–36.

    Google Scholar 

  137. Dröge, W. Free radicals in the physiological control of cell function. Physiol. Rev. 2002, 82, 47–95.

    Google Scholar 

  138. Wolff, S. P.; Jiang, Z. Y.; Hunt, J. V. Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic. Biol. Med. 1991, 10, 339–352.

    Google Scholar 

  139. Nishikawa, T.; Edelstein, D.; Du, X. L.; Yamagishi, S.; Matsumura, T.; Kaneda, Y.; Yorek, M. A.; Beebe, D.; Oates, P. J.; Hammes, H. P. et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000, 404, 787–790.

    Google Scholar 

  140. Di Meo, S.; Reed, T. T.; Venditti, P.; Victor, V. M. Role of ROS and RNS sources in physiological and pathological conditions. Oxid. Med. Cell. Longev. 2016, 2016, Article ID 1245049.

    Google Scholar 

  141. Ha, H.; Kim, K. H. Pathogenesis of diabetic nephropathy: The role of oxidative stress and protein kinase C. Diabetes Res. Clin. Pract. 1999, 45, 147–151.

    Google Scholar 

  142. Thompson, K. H.; Godin, D. V. Micronutrients and antioxidants in the progression of diabetes. Nutr. Res. 1995, 15, 1377–1410.

    Google Scholar 

  143. Newsholme, P.; Cruzat, V. F.; Keane, K. N.; Carlessi, R.; de Bittencourt, P. I., Jr. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem. J. 2016, 473, 4527–4550.

    Google Scholar 

  144. Jahani, M.; Shokrzadeh, M.; Vafaei–Pou, Z.; Zamani, E.; Shaki, F. Potential role of cerium oxide nanoparticles for attenuation of diabetic nephropathy by inhibition of oxidative damage. Asian J. Anim. Vet. Adv. 2016, 11, 226–234.

    Google Scholar 

  145. BarathManiKanth, S.; Kalishwaralal, K.; Sriram, M.; Pandian, S. R. K.; Youn, H. S.; Eom, S.; Gurunathan, S. Anti–oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice. J. Nanobiotechnology 2010, 8, 16.

    Google Scholar 

  146. Dkhil, M. A.; Zrieq, R.; Al–Quraishy, S.; Abdel Moneim, A. E. Selenium nanoparticles attenuate oxidative stress and testicular damage in streptozotocin–induced diabetic rats. Molecules 2016, 21, 1517.

    Google Scholar 

  147. Al–Quraishy, S.; Dkhil, M. A.; Abdel Moneim, A. E. Anti–hyperglycemic activity of selenium nanoparticles in streptozotocin–induced diabetic rats. Int. J. Nanomedicine 2015, 10, 6741–6756.

    Google Scholar 

  148. Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M. T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007, 39, 44–84.

    Google Scholar 

  149. Alexander, R. W. Hypertension and the pathogenesis of atherosclerosis. Hypertension 1995, 25, 155–161.

    Google Scholar 

  150. Kinscherf, R.; Deigner, H. P.; Usinger, C.; Pill, J.; Wagner, M.; Kamencic, H.; Hou, D.; Chen, M.; Schmiedt, W.; Schrader, M. et al. Induction of mitochondrial manganese superoxide dismutase in macrophages by oxidized LDL: Its relevance in atherosclerosis of humans and heritable hyperlipidemic rabbits. FASEB J. 1997, 11, 1317–1328.

    Google Scholar 

  151. Kinscherf, R.; Wagner, M.; Kamencic, H.; Bonaterra, G. A.; Hou, D. M.; Schiele, R. A.; Deigner, H. P.; Metz, J. Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits. Atherosclerosis 1999, 144, 33–39.

    Google Scholar 

  152. Yang, X. Y.; Li, Y.; Li, Y. D.; Ren, X. M.; Zhang, X. Y.; Hu, D.; Gao, Y. H.; Xing, Y. W.; Shang, H. C. Oxidative stress–mediated atherosclerosis: Mechanisms and therapies. Front. Physiol. 2017, 8, 600.

    Google Scholar 

  153. Wan, W. L.; Lin, Y. J.; Chen, H. L.; Huang, C. C.; Shih, P. C.; Bow, Y. R.; Chia, W. T.; Sung, H. W. In situ nanoreactor for photosynthesizing H2 gas to mitigate oxidative stress in tissue inflammation. J. Am. Chem. Soc. 2017, 139, 12923–12926.

    Google Scholar 

  154. Reczek, C. R.; Chandel, N. S. The two faces of reactive oxygen species in cancer. Annu. Rev. Cancer Biol. 2017, 1, 79–98.

    Google Scholar 

  155. Morgan, M. J.; Liu, Z. G. Crosstalk of reactive oxygen species and NF–κB signaling. Cell Res. 2011, 21, 103–115.

    Google Scholar 

  156. Weinberg, F.; Hamanaka, R.; Wheaton, W. W.; Weinberg, S.; Joseph, J.; Lopez, M.; Kalyanaraman, B.; Mutlu, G. M.; Budinger, G. R. S.; Chandel, N. S. Mitochondrial metabolism and ROS generation are essential for Kras–mediated tumorigenicity. Proc. Natl. Acad. Sci. USA 2010, 107, 8788–8793.

    Google Scholar 

  157. Ye, J. B.; Fan, J.; Venneti, S.; Wan, Y. W.; Pawel, B. R.; Zhang, J.; Finley, L. W. S.; Lu, C.; Lindsten, T.; Cross, J. R. et al. Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 2014, 4, 1406–1417.

    Google Scholar 

  158. Huang, L. E.; Arany, Z.; Livingston, D. M.; Bunn, H. F. Activation of hypoxia–inducible transcription factor depends primarily upon redox–sensitive stabilization of its α subunit. J. Biol. Chem. 1996, 271, 32253–32259.

    Google Scholar 

  159. Nelson, K. K.; Melendez, J. A. Mitochondrial redox control of matrix metalloproteinases. Free Radic. Biol. Med. 2004, 37, 768–784.

    Google Scholar 

  160. Diaz, B.; Shani, G.; Pass, I.; Anderson, D.; Quintavalle, M.; Courtneidge, S. A. Tks5–dependent, nox–mediated generation of reactive oxygen species is necessary for invadopodia formation. Sci. Signal. 2009, 2, ra53.

    Google Scholar 

  161. Giannoni, E.; Fiaschi, T.; Ramponi, G.; Chiarugi, P. Redox regulation of anoikis resistance of metastatic prostate cancer cells: Key role for Src and EGFR–mediated pro–survival signals. Oncogene 2009, 28, 2074–2086.

    Google Scholar 

  162. Morry, J.; Ngamcherdtrakul, W.; Yantasee, W. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles. Redox Biol. 2017, 11, 240–253.

    Google Scholar 

  163. Prylutska, S.; Grynyuk, I.; Matyshevska, O.; Prylutskyy, Y.; Evstigneev, M.; Scharff, P.; Ritter, U. C60 fullerene as synergistic agent in tumor–inhibitory doxorubicin treatment. Drugs R. D. 2014, 14, 333–340.

    Google Scholar 

  164. Giri, S.; Karakoti, A.; Graham, R. P.; Maguire, J. L.; Reilly, C. M.; Seal, S.; Rattan, R.; Shridhar, V. Nanoceria: A rare–earth nanoparticle as a novel anti–angiogenic therapeutic agent in ovarian cancer. PLoS One 2013, 8, e54578.

    Google Scholar 

  165. Vassie, J. A.; Whitelock, J. M.; Lord, M. S. Endocytosis of cerium oxide nanoparticles and modulation of reactive oxygen species in human ovarian and colon cancer cells. Acta Biomater. 2017, 50, 127–141.

    Google Scholar 

  166. Vassie, J. A.; Whitelock, J. M.; Lord, M. S. Targeted delivery and redox activity of folic acid–functionalized nanoceria in tumor cells. Mol. Pharm. 2018, 15, 994–1004.

    Google Scholar 

  167. Alili, L.; Sack, M.; von Montfort, C.; Giri, S.; Das, S.; Carroll, K. S.; Zanger, K.; Seal, S.; Brenneisen, P. Downregulation of tumor growth and invasion by redoxactive nanoparticles. Antioxid. Redox Signal. 2013, 19, 765–778.

    Google Scholar 

  168. Hijaz, M.; Das, S.; Mert, I.; Gupta, A.; Al–Wahab, Z.; Tebbe, C.; Dar, S.; Chhina, J.; Giri, S.; Munkarah, A. et al. Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer. BMC Cancer 2016, 16, 220.

    Google Scholar 

  169. Lin, T. S.; Zhao, X. Z.; Zhao, S.; Yu, H.; Cao, W. M.; Chen, W.; Wei, H.; Guo, H. Q. O2–generating MnO2 nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia. Theranostics 2018, 8, 990–1004.

    Google Scholar 

  170. Zhu, W. W.; Dong, Z. L.; Fu, T. T.; Liu, J. J.; Chen, Q.; Li, Y. G.; Zhu, R.; Xu, L. G.; Liu, Z. Modulation of hypoxia in solid tumor microenvironment with MnO2 nanoparticles to enhance photodynamic therapy. Adv. Funct. Mater. 2016, 26, 5490–5498.

    Google Scholar 

Download references

Acknowledgements

This work was supported, in part, by the University of Wisconsin-Madison, the National Institutes of Health (No. NIBIB/NCI P30CA014520) and the Brazilian Science without Borders Program (No. SwB-CNPq).

Author information

Authors and Affiliations

  1. Department of Radiology, University of Wisconsin-Madison, Madison, WI, 53705, USA

    Carolina A. Ferreira, Dalong Ni, Zachary T. Rosenkrans & Weibo Cai

Authors
  1. Carolina A. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dalong Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zachary T. Rosenkrans
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Weibo Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dalong Ni or Weibo Cai.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferreira, C.A., Ni, D., Rosenkrans, Z.T. et al. Scavenging of reactive oxygen and nitrogen species with nanomaterials. Nano Res. 11, 4955–4984 (2018). https://doi.org/10.1007/s12274-018-2092-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-018-2092-y

Keywords

Search

Navigation