We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Cerium oxide nanoparticles: applications and prospects in nanomedicine

    Soumen Das

    Advanced Materials Processing Analysis Center, Nanoscience Technology Center, University of Central Florida, Orlando, FL, USA

    Authors contributed equally

    Search for more papers by this author

    ,
    Janet M Dowding

    Burnett School of Biomedical Science, University of Central Florida, Orlando, FL, USA

    ,
    Kathryn E Klump

    Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

    ,
    James F McGinnis

    Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

    Department of Ophthalmology, Dean A McGee Eye Institute, University of Oklahoma Health Sciences Center, 608 Stanton L Young Blvd, Oklahoma City, OK 73104, USA

    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

    ,
    William Self

    Burnett School of Biomedical Science, University of Central Florida, Orlando, FL, USA

    &
    Sudipta Seal

    * Author for correspondence

    Material Science & Engineering, University of Central Florida, FL, USA.

    College of Medicine, University of Central Florida, FL, USA

    Published Online:https://doi.org/10.2217/nnm.13.133

    Promising results have been obtained using cerium (Ce) oxide nanoparticles (CNPs) as antioxidants in biological systems. CNPs have unique regenerative properties owing to their low reduction potential and the coexistence of both Ce3+/Ce4+ on their surfaces. Defects in the crystal lattice due to the presence of Ce3+ play an important role in tuning the redox activity of CNPs. The surface Ce3+:Ce4+ ratio is influenced by the microenvironment. Therefore, the microenvironment and synthesis method adopted also plays an important role in determining the biological activity and toxicity of CNPs. The presence of a mixed valance state plays an important role in scavenging reactive oxygen and nitrogen species. CNPs are found to be effective against pathologies associated with chronic oxidative stress and inflammation. CNPs are well tolerated in both in vitro and in vivo biological models, which makes CNPs well suited for applications in nanobiology and regenerative medicine.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    References

    • Kaplan J. Active oxygen. Nature159(4046),673 (1947).
    • Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol.7(1),65–74 (2009).
    • Drew B, Leeuwenburgh C. Aging and the role of reactive nitrogen species. Ann. NY Acad. Sci.959,66–81 (2002).
    • Hutson S. Experts urge a more measured look at antioxidants. Nat. Med.14(8),795–795 (2008).
    • Frankel EN, Finley JW. How to standardize the multiplicity of methods to evaluate natural antioxidants. J. Agric. Food Chem.56(13),4901–4908 (2008).
    • Erica S, Daniel A, Silvana A. Artificial nanoparticle antioxidants. In: Oxidative Stress: Diagnostics, Prevention, and Therapy. American Chemical Society, DC, USA, 235–253 (2011).
    • Sun C, Li H, Chen L. Nanostructured ceria-based materials: synthesis, properties, and applications. Energy Environ. Sci.5(9),8475–8505 (2012).
    • Deshpande S, Patil S, Kuchibhatla SV, Seal S. Size dependency variation in lattice parameter and valency states in nanocrystalline cerium oxide. Appl. Phys. Lett.87(13),133113 (2005).
    • Korsvik C, Patil S, Seal S, Self WT. Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem. Commun.10,1056–1058 (2007).▪ First paper to show that cerium oxide nanoparticles (CNPs) have superoxide dismutase mimetic activity.
    • 10  Karakoti A, Singh S, Dowding JM, Seal S, Self WT. Redox-active radical scavenging nanomaterials. Chem. Soc. Rev.39(11),4422–4432 (2010).
    • 11  Karakoti AS, Munusamy P, Hostetler K et al. Preparation and characterization challenges to understanding environmental and biological impacts of ceria nanoparticles. Surf. Interface Anal.44(8),882–889 (2012).▪▪ Nanoparticle synthesis parameters, storage and handling are very important for use in biological science/medicine. Summarizes the possible challenges for potential CNP use.
    • 12  Dowding JM, Das S, Kumar A et al. Cellular interaction and toxicity depend on physicochemical properties and surface modification of redox-active nanomaterials. ACS Nano7(6),4855–4868 (2013).
    • 13  Lynch I, Dawson KA. Protein–nanoparticle interactions. Nano Today3(1),40–47 (2008).
    • 14  Das S, Singh S, Dowding JM et al. The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments. Biomaterials33(31),7746–7755 (2012).
    • 15  Alili L, Sack M, Von Montfort C et al. Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid. Redox Signal. doi:10.1089/ars.2012.4831 (2012) (Epub ahead of print).
    • 16  Ji Z, Wang X, Zhang H et al. Designed synthesis of CeO2 nanorods and nanowires for studying toxicological effects of high aspect ratio nanomaterials. ACS Nano6(6),5366–5380 (2012).
    • 17  Tarantola M, Pietuch A, Schneider D et al. Toxicity of gold-nanoparticles: synergistic effects of shape and surface functionalization on micromotility of epithelial cells. Nanotoxicology5(2),254–268 (2011).
    • 18  Das S, Singh S, Singh V et al. Oxygenated functional group density on graphene oxide: its effect on cell toxicity. Part. Part. Syst. Char.30(2),148–157 (2013).
    • 19  Celardo I, De Nicola M, Mandoli C, Pedersen JZ, Traversa E, Ghibelli L. Ce3+ ions determine redox-dependent anti-apoptotic effect of cerium oxide nanoparticles. ACS Nano5(6),4537–4549 (2011).
    • 20  Asati A, Santra S, Kaittanis C, Perez JM. Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano4(9),5321–5331 (2010).
    • 21  Vincent A, Babu S, Heckert E et al. Protonated nanoparticle surface governing ligand tethering and cellular targeting. ACS Nano3(5),1203–1211 (2009).
    • 22  Wang X, Zhang D, Li Y et al. Self-doped Ce3+ enhanced CeO2 host matrix for energy transfer from Ce3+ to Tb3+. RSC Adv.3,3623–3630 (2013).
    • 23  Kumar A, Babu S, Karakoti AS, Schulte A, Seal S. Luminescence properties of europium-doped cerium oxide nanoparticles: role of vacancy and oxidation states. Langmuir25(18),10998–11007 (2009).
    • 24  Kalyanaraman B, Darley-Usmar V, Davies KJ et al. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic. Biol. Med.52(1),1–6 (2012).
    • 25  Heckert EG, Karakoti AS, Seal S, Self WT. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials29(18),2705–2709 (2008).
    • 26  Kuchma MH, Komanski CB, Colon J et al. Phosphate ester hydrolysis of biologically relevant molecules by cerium oxide nanoparticles. Nanomedicine6(6),738–744 (2010).
    • 27  Pirmohamed T, Dowding JM, Singh S et al. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem. Commun.46(16),2736–2738 (2010).
    • 28  Dowding JM, Dosani T, Kumar A, Seal S, Self WT. Cerium oxide nanoparticles scavenge nitric oxide radical (·NO). Chem. Commun.48(40),4896–4898 (2012).▪ Reveals that CNPs can also scavenge reactive nitrogen species.
    • 29  Dowding JM, Seal S, Self WT. Cerium oxide nanoparticles accelerate the decay of peroxynitrite (ONOO-). Drug. Deliv. Transl. Res. doi:10.1007/s13346-013-0136-0 (2013) (Epub ahead of print).
    • 30  Flora SJ. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid. Med. Cell. Longev.2(4),191–206 (2009).
    • 31  Melov S, Ravenscroft J, Malik S et al. Extension of life-span with superoxide dismutase/catalase mimetics. Science289(5484),1567–1569 (2000).
    • 32  Salvemini D, Mazzon E, Dugo L et al. Pharmacological manipulation of the inflammatory cascade by the superoxide dismutase mimetic, M40403. Br. J. Pharmacol.132(4),815–827 (2001).
    • 33  Rong Y, Doctrow SR, Tocco G, Baudry M. EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology. Proc. Natl Acad. Sci. USA96(17),9897–9902 (1999).
    • 34  Schubert D, Dargusch R, Raitano J, Chan SW. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. Res. Commun.342(1),86–91 (2006).
    • 35  Estevez A, Pritchard S, Harper K et al. Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic. Biol. Med.51(6),1155–1163 (2011).
    • 36  Niu J, Azfer A, Rogers LM, Wang X, Kolattukudy PE. Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc. Res.73(3),549–559 (2007).
    • 37  Colon J, Herrera L, Smith J et al. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine5(2),225–231 (2009).
    • 38  Wang IC, Tai LA, Lee DD et al. C(60) and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J. Med. Chem.42(22),4614–4620 (1999).
    • 39  Xue Y, Luan Q, Yang D, Yao X, Zhou K. Direct evidence for hydroxyl radical scavenging activity of cerium oxide nanoparticles. J. Phys. Chem. C115(11),4433–4438 (2011).
    • 40  Singh S, Dosani T, Karakoti AS, Kumar A, Seal S, Self WT. A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials32(28),6745–6753 (2011).
    • 41  Wason MS, Colon J, Das S et al. Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production. Nanomedicine9(4),558–569 (2012).
    • 42  Wang X, Zhang D, Li Y et al. Self-doped Ce3+ enhanced CeO2 host matrix for energy transfer from Ce3+ to Tb3+. RSC Adv.3,3623–3630 (2013).
    • 43  Yokel RA, Tseng MT, Dan M et al. Biodistribution and biopersistence of ceria engineered nanomaterials: size dependence. Nanomedicine9(3),398–407 (2012).
    • 44  Singh S, Kumar A, Karakoti A, Seal S, Self WT. Unveiling the mechanism of uptake and sub-cellular distribution of cerium oxide nanoparticles. Mol. BioSystems6(10),1813–1820 (2010).
    • 45  Giri S, Karakoti A, Graham RP et al. Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer. PLoS One8(1),e54578 (2013).
    • 46  Yokel RA, Au TC, Macphail R et al. Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats. Toxicol. Sci.127(1),256–268 (2012).
    • 47  Xia T, Kovochich M, Liong M et al. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano2(10),2121–2134 (2008).
    • 48  Clark A, Zhu A, Sun K, Petty HR. Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis. J. Nanopart. Res.13(10),5547–5555 (2011).
    • 49  Hirst SM, Karakoti AS, Tyler RD, Sriranganathan N, Seal S, Reilly CM. Anti-inflammatory properties of cerium oxide nanoparticles. Small5(24),2848–2856 (2009).
    • 50  Amin KA, Hassan MS, Awad el-ST, Hashem KS. The protective effects of cerium oxide nanoparticles against hepatic oxidative damage induced by monocrotaline. Int. J. Nano.6,143–149 (2011).
    • 51  Niu J, Wang K, Kolattukudy PE. Cerium oxide nanoparticles inhibits oxidative stress and nuclear factor-κB activation in H9c2 cardiomyocytes exposed to cigarette smoke extract. J. Pharmacol. Exp. Ther.338(1),53–61 (2011).
    • 52  Madero-Visbal RA, Alvarado BE, Colon JF et al. Harnessing nanoparticles to improve toxicity after head and neck radiation. Nanomedicine8(7),1223–1231 (2012).
    • 53  Briggs A, Corde S, Oktaria S et al. Cerium oxide nanoparticles: influence of the high-Z component revealed on radioresistant 9L cell survival under x-ray irradiation. Nanomedicine doi:10.1016/j.nano.2013.02.008 (2013) (Epub ahead of print).
    • 54  Zholobak NM, Ivanov VK, Shcherbakov AB et al. UV-shielding property, photocatalytic activity and photocytotoxicity of ceria colloid solutions. J. Photochem. Photobiol. B Biol.102(1),32–38 (2011).
    • 55  Babu S, Cho J-H, Dowding JM et al. Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging and therapeutics. Chem. Commun.46(37),6915–6917 (2010).
    • 56  Renu G, Rani V, Nair S, Subramanian K, Lakshmanan VK. Development of cerium oxide nanoparticles and its cytotoxicity in prostate cancer cells. Adv. Sci. Lett.6(1),17–25 (2012).
    • 57  Alili L, Sack M, Karakoti AS et al. Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor–stroma interactions. Biomaterials32(11),2918–2929 (2011).
    • 58  Ellison A, Fry R, Merchant S et al. Engineered oxide nanoparticles protect against neuronal damage associated with in vitro trauma. J. Neurotrauma10(20),1105 (2003).
    • 59  Callahan P, Colon J, Merchant S et al. Deleterious effects of microglia activated by in vi-tro trauma are blocked by engineered oxide nanoparticles. J. Neurotrauma20(10),1057 (2003).
    • 60  Das M, Patil S, Bhargava N et al. Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials28(10),1918–1925 (2007).
    • 61  Dangelo B, Santucci S, Benedetti E et al. Cerium oxide nanoparticles trigger neuronal survival in a human Alzheimer disease model by modulating BDNF pathway. Curr. Neurosci.5(2),167–176 (2009).
    • 62  Cimini A, D’angelo B, Das S et al. Antibody-conjugated PEGylated cerium oxide nanoparticles for specific targeting of Aβ aggregates modulate neuronal survival pathways. Acta Biomater.8(6),2056–2067 (2012).▪ Targeted nanoparticles are more efficient in mitigating oxidative stress-induced damage.
    • 63  Kim CK, Kim T, Choi IY et al. Ceria Nanoparticles that can protect against ischemic stroke. Angew. Chem. Int. Ed. Engl.124(44),11201–11205 (2012).
    • 64  Estevez A, Erlichman J. Cerium oxide nanoparticles for the treatment of neurological oxidative stress diseases. Brain28,30 (2011).
    • 65  Decoteau W, Estevez A, Leo-Nyquist S, Heckman K, Reed K, Erlichman J. Ceria nanoparticles reduce disease severity in a mouse model of multiple sclerosis. Presented at: TechConnect World Conference and Expo 2011. Boston, MA, USA, 13–16 June 2011.
    • 66  Chen J, Patil S, Seal S, McGinnis JF. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat. Nanotechnol.1(2),142–150 (2006).▪▪ Demonstrates that CNPs, in a concentration-dependent manner, protect normal retinal neurons in vitro and in vivo against intracellularly generated reactive oxygen species.
    • 67  Zhou X, Wong LL, Karakoti AS, Seal S, McGinnis JF. Nanoceria inhibit the development and promote the regression of pathologic retinal neovascularization in the VLDLR knockout mouse. PLoS One6(2),e16733 (2011).▪▪ Demonstrates that a single 172-ng injection of CNPs can regress inherited pathological vascular lesions in vivo in a mammalian retina.
    • 68  Cai X, Sezate SA, Seal S, McGinnis JF. Sustained protection against photoreceptor degeneration in tubby mice by intravitreal injection of nanoceria. Biomaterials33(34),8771–8781 (2012).
    • 69  Kong L, Cai X, Zhou X et al. Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways. Neurobiol. Dis.42(3),514–523 (2011).
    • 70  Klump K, Seal S, Dyer M, McGinnis J. In vivo targeting and inhibition of retinoblastoma with catalytic antioxidants. Presented at: International Society for Eye Research. Berlin, Germany, 21–25 July 2012.
    • 71  Pierscionek BK, Li Y, Schachar RA, Chen W. The effect of high concentration and exposure duration of nanoceria on human lens epithelial cells. Nanomedicine8(3),383–390 (2012).
    • 72  Wong LL, Hirst SM, Pye QN, Reilly CM, Seal S, McGinnis JF. Catalytic nanoceria are preferentially retained in the rat retina and are not cytotoxic after intravitreal injection. PLoS One8(3),e58431 (2013).
    • 73  Karakoti AS, Tsigkou O, Yue S et al. Rare earth oxides as nanoadditives in 3-D nanocomposite scaffolds for bone regeneration. J. Mater. Chem.20(40),8912–8919 (2010).
    • 74  Mandoli C, Pagliari F, Pagliari S et al. Stem cell aligned growth induced by CeO2 nanoparticles in PLGA scaffolds with improved bioactivity for regenerative medicine. Adv. Function. Mater.20(10),1617–1624 (2010).
    • 75  Chigurupati S, Mughal MR, Okun E et al. Effects of cerium oxide nanoparticles on the growth of keratinocytes, fibroblasts and vascular endothelial cells in cutaneous wound healing. Biomaterials34(9),2194–2201 (2013).
    • 76  Davan R, Prasad R, Jakka VS et al. Cerium oxide nanoparticles promotes wound healing activity in in-vivo animal model. J. Bionanosci.6(2),78–83 (2012).
    • 77  Pagliari F, Mandoli C, Forte G et al. Cerium oxide nanoparticles protect cardiac progenitor cells from oxidative stress. ACS Nano6(5),3767–3775 (2012).
    • 78  Chaudhury K, Babu NK, Das S, Kumar A, Seal S. Mitigation of endometriosis using regenerative cerium oxide nanoparticles. Nanomedicine9(3),439–448 (2013).
    • 79  Pourkhalili N, Hosseini A, Nili-Ahmadabadi A et al. Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. World J. Diabetes2(11),204–210 (2011).
    • 80  Cassee FR, Campbell A, Boere AJF et al. The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice. Environ. Res.115,1–10 (2012).
    • 81  Arnold M, Badireddy A, Wiesner M, Di Giulio R, Meyer J. Cerium oxide nanoparticles are more toxic than equimolar bulk cerium oxide in Caenorhabditis elegans.Arch. Environ. Contamin. Toxicol.65(2),224–233 (2013).
    • 82  Zhang H, He X, Zhang Z et al. Nano-CeO2 exhibits adverse effects at environmental relevant concentrations. Environ. Sci. Technol.45(8),3725–3730 (2011).
    • 83  Tseng MT, Lu X, Duan X et al. Alteration of hepatic structure and oxidative stress induced by intravenous nanoceria. Toxicol. Appl. Pharmacol.260(2),173–182 (2012).
    • 84  Lin W, Huang Y-W, Zhou X-D, Ma Y. Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int. J. Toxicol.25(6),451–457 (2006).
    • 85  Hardas SS, Butterfield DA, Sultana R et al. Brain distribution and toxicological evaluation of a systemically delivered engineered nanoscale ceria. Toxicol. Sci.116(2),562–576 (2010).
    • 86  Demokritou P, Gass S, Pyrgiotakis G et al. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO2 inhalation exposures. Nanotoxicology doi:10.3109/17435390.2012.739665 (2012) (Epub ahead of print).
    • 87  Hardas SS, Butterfield DA, Sultana R et al. Brain distribution and toxicological evaluation of a systemically delivered engineered nanoscale ceria. Toxicol. Sci.116(2),562–576 (2010).
    • 88  Ma Y, Kuang L, He X et al. Effects of rare earth oxide nanoparticles on root elongation of plants. Chemosphere78(3),273–279 (2010).
    • 89  Zhang P, Ma Y, Zhang Z et al. Biotransformation of ceria nanoparticles in cucumber plants. ACS Nano6(11),9943–9950 (2012).
    • 90  Karakoti AS, Singh S, Kumar A et al. PEGylated nanoceria as radical scavenger with tunable redox chemistry. J. Am. Chem. Soc.131(40),14144–14145 (2009).
    • 91  De Marzi L, Monaco A, De Lapuente J et al. Cytotoxicity and genotoxicity of ceria nanoparticles on different cell lines in vitro. Int. J. Mol. Sci.14(2),3065–3077 (2013).
    • 92  Pelletier DA, Suresh AK, Holton GA et al. Effects of engineered cerium oxide nanoparticles on bacterial growth and viability. Appl. Environ. Microbiol.76(24),7981–7989 (2010).
    • 93  Dan M, Tseng MT, Wu P, Unrine JM, Grulke EA, Yokel RA. Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial. Int. J. Nanomedicine7,4023–4036 (2012).
    • 94  Rojas S, Gispert JD, Abad S et al.In vivo biodistribution of amino-functionalized ceria nanoparticles in rats using positron emission tomography. Mol. Pharm.9(12),3543–3550 (2012).
    • 95  Safi M, Sarrouj H, Sandre O, Mignet N, Berret JF. Interactions between sub-10-nm iron and cerium oxide nanoparticles and 3T3 fibroblasts: the role of the coating and aggregation state. Nanotechnology21(14),145103 (2010).
    • 96  Gojova A, Lee JT, Jung HS, Guo B, Barakat AI, Kennedy IM. Effect of cerium oxide nanoparticles on inflammation in vascular endothelial cells. Inhal. Toxicol.21(S1),123–130 (2009).
    • 97  Raemy DO, Limbach LK, Rothen-Rutishauser B et al. Cerium oxide nanoparticle uptake kinetics from the gas-phase into lung cells in vitro is transport limited. Eur. J. Pharm. Biopharm.77(3),368–375 (2011).
    • 98  Xue Y, Zhai Y, Zhou K et al. The vital role of buffer anions in the antioxidant activity of CeO2 nanoparticles. Chemistry18(35),11115–11122 (2012).
    • 99  Tarnuzzer RW, Colon J, Patil S, Seal S. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett.5(12),2573–2577 (2005).▪ Demonstrates that CNPs significantly decrease radiation damage by scavenging reactive oxygen species in normal cell lines while inducing cancer death.
    • 100  Srinivas A, Rao PJ, Selvam G, Murthy PB, Reddy PN. Acute inhalation toxicity of cerium oxide nanoparticles in rats. Toxicol. Lett.205(2),105–115 (2011).
    • 101  Horie M, Nishio K, Kato H et al. Cellular responses induced by cerium oxide nanoparticles: induction of intracellular calcium level and oxidative stress on culture cells. J. Biochem.150(4),461–471 (2011).
    • 102  He X, Zhang H, Ma Y et al. Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation. Nanotechnology21(28),285103 (2010).
    • 103  Lee T-L, Raitano JM, Rennert OM, Chan SW, Chan WY. Accessing the genomic effects of naked nanoceria in murine neuronal cells. Nanomedicine8(5),599–608 (2012).
    • 104  Rodea-Palomares I, Gonzalo S, Santiago-Morales J et al. An insight into the mechanisms of nanoceria toxicity in aquatic photosynthetic organisms. Aquat. Toxicol.122–123,133–143 (2012).
    • 105  Hussain S, Al-Nsour F, Rice AB et al. Cerium dioxide nanoparticles induce apoptosis and autophagy in human peripheral blood monocytes. ACS Nano6(7),5820–5829 (2012).
    • 106  Zhao L, Peng B, Hernandez-Viezcas JA et al. Stress response and tolerance of zea mays to CeO2 nanoparticles: cross talk among H2O2, heat shock protein, and lipid peroxidation. ACS Nano6(11),9615–9622 (2012).