Nanomaterials in Antioxidant Research

  • Aditya Arya
  • Anamika Gangwar
  • Narendra Kumar SharmaEmail author


Oxidative stress is proposed as leading event in the deterioration of health and basic biological processes. Ever since the Harman’s theory of aging was proposed based on the ill effects of oxidative in the body, the pace of oxidative stress research became rapid. The antioxidants were proposed as putative therapeutic and prophylactic agents for the prevention of oxidative damage and its aftermath. Despite the escalating research publications in the domain of oxidative stress and antioxidant therapy, apparent clinical transitions are fairly low. Perhaps, this should not be looked as question on the studies which were performed on the antioxidants, rather our poor understanding of cross talk of antioxidants and oxidants in the cells and its downstream effects. It seems that decision of considering antioxidants as miracle drugs for aging and similar condition was too early. There is lot more to be explored in this domain, and as we move deeper, we realize that oxidative stress and antioxidant interplay is one of the most complicated biological events that has several fold more complexity than basic cellular processes and metabolism. The scientific questions such as how much antioxidant dose is optimal and which antioxidant is most suitable can only be answered in a context-specific manner. The several anomalies and unfruitful clinical translations of antioxidants have led to the continuation and intensification of antioxidant research. With the advent of a new domain of science named nanotechnology, few exciting possibilities have emerged in the antioxidant researches which are likely to answer some of the issues of conventional antioxidants. This chapter is aimed to discuss the emerging trends in nano-antioxidants with a special focus on much-studied antioxidant nanoceria.


  1. Arya A, Sethy NK, et al. Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation. Int J Nanomedicine. 2013;8:4507–20.PubMedPubMedCentralGoogle Scholar
  2. Arya A, Sethy NK, et al. Cerium oxide nanoparticles prevent apoptosis in primary cortical culture by stabilizing mitochondrial membrane potential. Free Radic Res. 2014;48(7):784–93.CrossRefPubMedGoogle Scholar
  3. Arya A, Gangwar A, et al. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK-PKC-CBP signaling cascade. Int J Nanomedicine. 2016;11:1159–73.PubMedPubMedCentralGoogle Scholar
  4. Asati A, Santra S, et al. Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angew Chem Int Ed Engl. 2009;48(13):2308–12.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Azam S, Hadi N, et al. Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties. Toxicol In Vitro. 2004;18(5):555–61.CrossRefPubMedGoogle Scholar
  6. Babior BM. NADPH oxidase: an update. Blood. 1999;93(5):1464–76.PubMedGoogle Scholar
  7. Beal MF, Ferrante RJ, et al. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol. 1997;42(4):644–54.CrossRefPubMedGoogle Scholar
  8. Bouayed J, Bohn T. Exogenous antioxidants–double-edged swords in cellular redox state: health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxidative Med Cell Longev. 2010;3(4):228–37.CrossRefGoogle Scholar
  9. Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29(3–4):222–30.CrossRefPubMedGoogle Scholar
  10. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A. 1976;73(10):3685–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Campbell CT, Peden CH. Chemistry. Oxygen vacancies and catalysis on ceria surfaces. Science. 2005;309(5735):713–4.CrossRefPubMedGoogle Scholar
  12. Catoni C, Peters A, et al. Life history trade-offs are influenced by the diversity, availability and interactions of dietary antioxidants. Anim Behav. 2008;76:12.CrossRefGoogle Scholar
  13. Chen J, Patil S, et al. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat Nanotechnol. 2006;1(2):142–50.CrossRefPubMedGoogle Scholar
  14. Chen S, Hou Y, et al. Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress. Biol Trace Elem Res. 2013;154(1):156–66.CrossRefPubMedGoogle Scholar
  15. Clark AJ, et al. Calicum microdomains form within neutrophils at the neutrophil-tumor cell synapse: role in antibody-dependent target cell apoptosis. Cancer Immunol Immunother. 2010;59(1):149–59.Google Scholar
  16. Colon J, et al. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine. 2009;5(2):225–31.Google Scholar
  17. Dalle-Donne I, Giustarini D, et al. Protein carbonylation in human diseases. Trends Mol Med. 2003;9(4):169–76.CrossRefPubMedGoogle Scholar
  18. Das S, Chigurupati S, et al. Therapeutic potential of nanoceria in regenerative medicine. MRS Bull. 2014;39(11):8.CrossRefGoogle Scholar
  19. De Minicis S, Brenner DA. NOX in liver fibrosis. Arch Biochem Biophys. 2007;462(2):266–72.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Decker EA. Phenolics: prooxidants or antioxidants? Nutr Rev. 1997;55(11 Pt 1):396–8.PubMedGoogle Scholar
  21. Deshpande S, Patil S, et al. Size dependency variation in lattice parameter and valency states in nanocrystalline cerium oxide. Appl Phys Lett. 2005;87(13):3.CrossRefGoogle Scholar
  22. Dowding JM, Dosani T, et al. Cerium oxide nanoparticles scavenge nitric oxide radical ( NO). Chem Commun (Camb). 2012;48(40):4896–8.CrossRefGoogle Scholar
  23. Esch F, Fabris S, et al. Electron localization determines defect formation on ceria substrates. Science. 2005;309(5735):752–5.CrossRefPubMedGoogle Scholar
  24. Estevez AY, Erlichman JS. The potential of cerium oxide nanoparticles (nanoceria) for neurodegenerative disease therapy. Nanomedicine (Lond). 2014;9(10):1437–40.CrossRefGoogle Scholar
  25. Figueroa, M.. Accessed 4 Mar 2014.
  26. Galati G, O’Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med. 2004;37(3):287–303.CrossRefPubMedGoogle Scholar
  27. Halliwell B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol. 2006;141(2):312–22.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hayat A, Andreescu D, et al. Redox reactivity of cerium oxide nanoparticles against dopamine. J Colloid Interface Sci. 2014;418:240–5.CrossRefPubMedGoogle Scholar
  29. Heckert EG, Karakoti AS, et al. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials. 2008;29(18):2705–9.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Heckman KL, DeCoteau W, et al. Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain. ACS Nano. 2013;7(12):10582–96.CrossRefPubMedGoogle Scholar
  31. Hirst SM, et al. Anti-inflammatory properties of cerium oxide nanoparticles. Small. 2009;5(24):2848–56.Google Scholar
  32. Hirst SM, Karakoti A, et al. Bio-distribution and in vivo antioxidant effects of cerium oxide nanoparticles in mice. Environ Toxicol. 2011;28(2):107–18.CrossRefPubMedGoogle Scholar
  33. Hirst SM, Karakoti A, et al. Bio-distribution and in vivo antioxidant effects of cerium oxide nanoparticles in mice. Environ Toxicol. 2013;28(2):107–18.CrossRefPubMedGoogle Scholar
  34. Hussain S, Al-Nsour F, et al. Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes. Int J Nanomedicine. 2012;7:1387–97.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kalyanaraman B. Teaching the basics of redox biology to medical and graduate students: oxidants, antioxidants and disease mechanisms. Redox Biol. 2013;1(1):244–57.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Karakoti AS, Monteiro-Riviere NA, et al. Nanoceria as antioxidant: synthesis and biomedical applications. JOM (1989). 2008;60(3):33–7.CrossRefGoogle Scholar
  37. Kohen R, Nyska A. Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol. 2002;30(6):620–50.CrossRefPubMedGoogle Scholar
  38. Lambeth JD. Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Radic Biol Med. 2007;43(3):332–47.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Mehlhorn I, et al. High-level expression and characterization of a purified 142-residue polypeptide of the prion protein. Biochemistry. 1996;35(17):5528–37.Google Scholar
  40. Molina RM, Konduru NV, et al. Bioavailability, distribution and clearance of tracheally instilled, gavaged or injected cerium dioxide nanoparticles and ionic cerium. Environ Sci Nano. 2014;1:13.CrossRefGoogle Scholar
  41. Niu J, Azfer A, et al. Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res. 2007;73(3):549–59.CrossRefPubMedGoogle Scholar
  42. Novo E, Parola M. Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair. 2008;1(1):5.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Pagliari F, et al. Cerium oxide nanoparticles protect cardiac progenitor cells from oxidative stress. ACS Nano. 2012;6(5):3767–75.Google Scholar
  44. Palozza P, Serini S, et al. Regulation of cell cycle progression and apoptosis by beta-carotene in undifferentiated and differentiated HL-60 leukemia cells: possible involvement of a redox mechanism. Int J Cancer. 2002;97(5):593–600.CrossRefPubMedGoogle Scholar
  45. Pirmohamed T, Dowding JM, et al. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem Commun (Camb). 2010;46(16):2736–8.CrossRefGoogle Scholar
  46. Prior RL, Cao G. In vivo total antioxidant capacity: comparison of different analytical methods. Free Radic Biol Med. 1999;27(11–12):1173–81.CrossRefPubMedGoogle Scholar
  47. Pritsos CA. Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system. Chem Biol Interact. 2000;129(1–2):195–208.CrossRefPubMedGoogle Scholar
  48. Radimer KL, Ballard-Barbash R, et al. Weight change and the risk of late-onset breast cancer in the original Framingham cohort. Nutr Cancer. 2004;49(1):7–13.CrossRefPubMedGoogle Scholar
  49. Reed K, Cormack CM, et al. Exploring the properties and applications of nancoeria: is there plenty of room at the bottom? Environ Sci Nano. 2014;1(1):14.Google Scholar
  50. Rhee SG, Chae HZ, et al. Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med. 2005;38(12):1543–52.CrossRefPubMedGoogle Scholar
  51. Rojkind M, Dominguez-Rosales JA, et al. Role of hydrogen peroxide and oxidative stress in healing responses. Cell Mol Life Sci. 2002;59(11):1872–91.CrossRefPubMedGoogle Scholar
  52. Schubert W, et al. Analyzing proteome topology and function by automated multidimensional fluorescence microscopy. Nat Biotechnol. 2006;24(10):1270–8.Google Scholar
  53. Soberman RJ. The expanding network of redox signaling: new observations, complexities, and perspectives. J Clin Invest. 2003;111(5):571–4.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Suzanne M, Steller H. Letting go: modification of cell adhesion during apoptosis. J Biol. 2009;8(5):49.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Tarnuzzer RW, et al. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett. 2005;5(12):2573–7.Google Scholar
  56. Tseng MT, et al. Persistent hepatic structural alterations following nanoceria vascular infusion in the rat. Toxicol Pathol. 2014;42(6):984–96.Google Scholar
  57. Ujjain SK, Das A, et al. Nanoceria based electrochemical sensor for hydrogen peroxide detection. Biointerphases. 2014;9(3):031011.CrossRefPubMedGoogle Scholar
  58. Vasquez-Vivar J, Kalyanaraman B. Generation of superoxide from nitric oxide synthase. FEBS Lett. 2000;481(3):305–6.CrossRefPubMedGoogle Scholar
  59. Vignais PV. The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci. 2002;59(9):1428–59.CrossRefPubMedGoogle Scholar
  60. Wason MS, Colon J, et al. Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production. Nanomedicine. 2013;9(4):558–69.CrossRefPubMedGoogle Scholar
  61. Willett WC, MacMahon B. Diet and cancer–an overview (second of two parts). N Engl J Med. 1984;310(11):697–703.CrossRefPubMedGoogle Scholar
  62. Williams RJ, Spencer JP, et al. Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med. 2004;36(7):838–49.CrossRefPubMedGoogle Scholar
  63. Winterbourn CC. Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol. 2008;4(5):278–86.CrossRefPubMedGoogle Scholar
  64. Yeh SL, Wang HM, et al. Interactions of beta-carotene and flavonoids on the secretion of pro-inflammatory mediators in an in vitro system. Chem Biol Interact. 2009;179(2–3):386–93.CrossRefPubMedGoogle Scholar
  65. Yokel RA, Au TC, et al. Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats. Toxicol Sci. 2012;127(1):256–68.CrossRefPubMedGoogle Scholar
  66. Yokel RA, Tseng MT, et al. Biodistribution and biopersistence of ceria engineered nanomaterials: size dependence. Nanomedicine. 2013;9(3):398–407.CrossRefPubMedGoogle Scholar
  67. Yokel RA, Hussain S, et al. The yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity. Environ Sci Nano. 2014;1(5):406–28.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Aditya Arya
    • 1
  • Anamika Gangwar
    • 1
  • Narendra Kumar Sharma
    • 2
    Email author
  1. 1.Peptide and Proteomics DivisionDefence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development OrganizationTimarpurIndia
  2. 2.Division of Infectious Diseases, Hospital São Paulo, Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil

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