Highlights
-
•
To synthesis the cerium oxide nanoparticles using different sources.
-
•
Biomedical applications of cerium oxide nanoparticles.
-
•
Applications of cerium oxide nanoparticles in toxicity studies.
Keywords: Cerium oxide nanoparticles, Synthesis, Antibacterial activity, Antioxidant activity, Toxicity
Abstract
A cerium oxide nanoparticles (nanoceria) has a wide range of applications in different fields, especially biomedical division. As a matter of concern, it has a major impact on the human health and environment. The aim of this review is to address the different ways of synthesis of nanoceria using chemical and green synthesis methods and characterization and the applications of nanoceria for antioxidant, anticancer, antibacterial activities and toxicological studies including the most recent studies carried out in vivo and in vitro to study the problems. We have exclusively discussed on the toxicology of nanoceria exposed to the general public along with recent advances in the studies of antimicrobial, toxicity and anti-oxidant activity.
1. Introduction
Cerium belongs to lanthanide series and is rare earth metal (atomic number = 58).It is the most abundant rare earth metal which is present in two oxidation states i.e. +3 and +4 [1]. Cerium oxide is considered to be a lanthanide metal oxide and is used as an ultraviolet absorber [2], [3], catalyst [4], [5], polishing agent, gas sensors etc [6], [7], [8], [9], [10]. For commercial purpose, nanoceria plays a vital role in cosmetic products, consumer products, instruments and high technology. Moreover, they behave as very good oxide ion conductors in case of solid oxide fuel cells and used as a material in the electrode for gas sensors [11].
Recently, the importance of biomedical applications is growing as they exhibit protection against radiation, cellular damage mediated by toxicants and during pathological conditions such as brain or cardiac ischemia, neurological disorders or neurodegeneration of retina [12]. Naked nanoceria has poor solubility in the water leading to complications in biological applications. Many studies have come out with the polymer coating of nanomaterials which enhances the stability, biocompatibility and water solubility e.g. nanoceria coated with dextran exhibits antioxidant property [13].
Due to the extensive use, nanoceria is getting released to the environment and exposure to humans (mostly via inhalation) is a major concern. Contradictory results are found in the literature reporting the toxicity of nanoceria. Few papers addressed nanoceria to have low toxicity [14]. and don’t mediate cytotoxicity or inflammation [15], [16]. On the contrary, evidence from literature also depicts nanoceria trigger cell death. They trigger pro-oxidative effect due to reactive oxygen species (ROS) which cause damage to the cell and ultimately lead to cell death. Some studies addressed induction of oxidative stress caused by nanoceria either in vitro or in vivo [17] whereas they act as direct antioxidants and behave as free radical scavengers. It occurs by the interaction of superoxide radical, hydroxyl radical and hydrogen peroxide which restricts cell death due to oxidative stress. In addition to this, controversial results are also seen regarding oxidative stress. Studies have shown nanoceria either to exhibit pro-oxidative properties or antioxidant properties [18], [19], [20].
In this review, we focus and discuss the chemical and green synthesis of nanoceria and the underlying mechanisms in several studies like antimicrobial, toxicity (human health) such as cytotoxicity, genotoxicity, neurotoxicity, antioxidant activities (in vivo & in vitro) and biomedical applications.
2. Synthesis of nanoceria
Synthesis of nanoceria can be prepared by two means i.e. chemical method and green synthesis.
2.1. Chemical method
Many chemical methods are reported by researchers for the synthesis of nanoceria. Different have proved the synthesis of nanoceria by precipitation method [21], [22], [23] like co-precipitation [24] and chemical precipitation [25], [26], microwave [27], [28], sonochemical [29], [30], hydrothermal [31], [32], [33], [34], reverse-co-precipitation [35], microwave-hydrothermal method [36].
A novel method for the synthesis of nanoceria is done by using the cage-shaped protein called apoferritin. It was a two and three-D array formation using this protein. For the synthesis of nanoceria, apoferritin was considered as bio-template. The chemical reaction occurred at the cavity. There was oxidation of trivalent cerium ions and led to the formation of nanoceria as seen in case of iron oxide formation. It was confirmed as nanoceria with size 5.0 ± 0.7 nmThere was salt bridge formation between the ferritins (each apoferritin containing a nanoparticle) by multivalent cerium ions. The best salt bridge formation led to a 2-D array of nanoceria containing ferritin and 3-D arrays acquiring ferritin with two different morphology i.e. Octahedral or prism structured [37].
2.2. Green method (from plant extracts)
The synthesis of nanoceria using different sources shown in Table 1.Nanoceria can also be synthesized by using green methods. There are many studies which have reported the green synthesis of nanoceria using Gloriosa superba L. leaf extract. The nanoparticles formed were confirmed by XRD and was found to be spherical in shape [38].
Table 1.
S. no | Synthesis route | Size | Applications | Reference |
---|---|---|---|---|
1 | co-precipitation method | 20 nm (TEM and XRD) | – | [24] |
2 | Commercial nanoceria | 8nmto 20 nm (TEM) | molecular mechanism of cytotoxicity on lung adenocarcinoma (A549) cells | [55] |
3 | hydrothermal process | 3.1 nm (TEM) | High oxidation activity | [34] |
4 | Fungal culture filtrate of Curvularia lunata | 5 to 20 nm (TEM) | Antibacterial activity against Gram positive (Staphylococcus aureus, Streptococcus pneumoniae and Bacillus subtilis) and three Gram negative bacteria (Pseudomonas aeruginosa, Proteus vulgaris and Klebsiella pneumoniae) | [39] |
5 | Leaves of Aloe barbadensis Miller plant | 63.6 nm (dynamic light scattering analysis) | – | [42] |
6 | Precipitation method using ammonia water and oxalic acid as precipitant | 100–300 nm (SEM) | – | [21] |
7 | Gloriosa superba L. leaf extract | 5 nm (TEM) | Antibacterial activity against both gram positive and gram-negative bacteria | [38] |
8 | Acalypha indica leaf extract | 25–30 nm (TEM and XRD) | Antibacterial activity | [41] |
9 | Olea europaea leaf extract | 24 nm (SEM and TEM) | Antibacterial and antifungal activity against Gram-positive (G + ve) (Staphylococcus aureus ATCC 6538) and Gram-negative (G−ve) (Escherichia coli ATCC 15224, Pseudomonas aeruginosa ATCC 15442, Klebsiella pneumoniae ATCC-BAA 1706) strains and Mucor species (FCBP-0300), Aspergillus flavus (FCBP-0064), Fusarium solani (FCBP-434), and Aspergillus niger (FCBP-0198) | [40] |
10 | Hibiscus Sabdariffa's floweraqueous extract | 3.9 nm (HR TEM and XRD) | Stability, surface morphology, chemical bonding and chemical valance states are studies | [43] |
11 | Fresh egg white | 25 nm (FE SEM) | non-toxic effect of concentration up to 800 μg/ml on human periodontal fibroblasts cells | [44] |
Another study also addressed the synthesis of nanoceria using culture filtrate of Curvularia lunata. This even confirmed the spherical shape of the nanoparticles which ranged from 5 to 20 nm [39]. These synthesis nanoparticles also exhibited antibacterial activities against different bacterial species. However, it was concluded that nanoparticles couldn’t penetrate the bacterial cells [40].
Recently, another study has also confirmed the use of Acalypha indica and Aloe vera plant leaf extract for the synthesis of nanoceria [41], [42]. These extracts were used as a capping agent for the synthesis. The most recent study of nanoceria synthesis is acquired by using the flower extract of Hibiscus sabdariffa as a chelating agent. The characterization of nanoceria confirmed the size to be approx. 3.9 nm in diameter [43].
2.3. Synthesis from nutrients
The green approach synthesis is widely accepted by the researchers due to its reliable and eco- friendly purpose. Several studies have reported the synthesis of nanoceria using different nutrients like egg white protein [44]. It has been proposed that ovalbumin and lysozyme are the two proteins of egg white which acted as stabilizing agent for the synthesis of nanoceria. The mechanism of nanoparticles formation can be explained by the electrostatic interaction held between the cerium ions (Ce3+) and protein with opposite charge enhances the growth along with small stable isotropic nanoparticle formation [45].
However, another study also reveals the synthesis of nanoceria using honey. The presence of vitamins, carbohydrates, and enzymes in the honey matrix structure possess hydroxyl and amine groups. Therefore, it was extensively used as stabilizing and coating agent to the cerium species along with nanoceria which inhibited their crystal growth [46].
3. Applications of nanoceria
Nanoceria is having a lot of applications in the biomedical field shown in Fig. 1.
3.1. Antibacterial activity
Many studies have confirmed that nanoceria also showed antibacterial activity against Pseudomonas aeruginosa through agar well diffusion and broth dilution method. The experimental data confirmed that there was a complete zone of inhibition in case of P.aeruginosa (NCIM-2242) with the increase in the concentration of nanoceria i.e. 500,750 and 1000 μg L−1 per well in case of agar well diffusion method. Moreover, with concentration 200 and 400 μg L−1 against P. aeruginosa (NCIM-2242) the antibacterial activity was confirmed by broth dilution method [47].
In addition to this, another study also addressed that at lower temperature antibacterial activity was seen including E.Coli, B.subtilis, Shewanellaoneidensis and Pseudokirchneriella supcapitata. The probable mechanism behind this activity was due to the action of reactive oxygen species (ROS) [48].
3.2. Toxicity studies (Impact on human health)
The impact of nanoceria in the human health has brought keen interest among the researchers. There are two main routes through which nanoceria are exposed to the public i.e. inhalation and ingestion. Moreover, the inhaled cerium exits the respiratory tract mediated by different pathways and at different rates which depend on the body fluids solubility [49], [50]. After the process of ingestion, cerium is excreted in the feces.
As nanoceria get poorly absorbed in the intestine, the exposure through inhalation is a major concern than ingestion. After the inhalation, the lungs and lymph nodes associated with it are the major targets. It may so happen that other organs might get affected. When the nanoceria get absorbed through circulation, it may also get distributed in other organs like liver, spleen, and kidney. Therefore, with variation in the size of nanoparticles can reach to different target areas of respiratory tract where it gets absorbed.
Researchers have also confirmed that nanoceria is poorly absorbed in the digestive system. Through oral route of exposure, the solubility of cerium oxide nanoparticle is very less when compared to other forms. So, it is probably thought that acute toxicity is less even though when transformed into soluble forms when absorbed by the body [51].
3.3. Cytotoxicity
Nanoceria was also the reason to cause cytotoxicity and oxidative stress. The 20 nm nanoceria was toxic towards cultured human lung cancer cells. Sulforhodamine B was used to check the cell viability when exposed to 3.5, 10.5 and 23.3 μg/ml of nanoceria for 24, 48 and 72 h. There was a decrease in cell viability with respect to the dosage of nanoparticles and exposure time.
There was a quantitative assessment of total ROS, malondialdehyde, α-tocopherol, glutathione and lactate dehydrogenase which were the indicators of oxidative stress and cytotoxicity. Ultimately, there was a reduced level of glutathione and α- tocopherol. Free radicals were generated due to nanoparticle exposure and increase in oxidative stress led to high level of lactate dehydrogenase and malondialdehyde which showed clear indication towards cell membrane damage and lipid peroxidation [52].
In addition to the above study, nanoceria also caused cytotoxicity towards prostate cancer cell lines (PC-3) which was confirmed by MTT assay. But these were non- toxic towards normal cell lines (L929). The fluorescent dye rhodamine-123 conjugated with nanoceria which confirmed the cellular uptake followed by the optical detection [53].
3.4. Genotoxicity
Human bronchial epithelial cells (BEAS-2B) were cultured in KGM (Keratinocyte growth medium) defined the medium. Comet assay confirmed that after 24 h the DNA single-strand broke when exposed to different concentrations of nanoceria (10,50,100,150 μg/ml) [54].
Recently, a study explained the molecular mechanism behind the toxicity of nanoceria on lung adenocarcinoma (A549) cells. These nanoparticles were solely responsible for morphological changes in A549 cells. Moreover, it led to cell apoptosis, due to increase in annexin–V positive cells and loss in mitochondrial membrane potential. These were confirmed by immunoblot analysis of BAX, Bcl-2, Cyt-C, AIF, caspase-3, and caspase-9. Hence, reactive oxygen species induced DNA damage and cell cycle arrest which caused apoptotic cell death in A549 cells due to nanoceria [55].
Another genotoxicity study was carried out in female albino Wistar rats when exposed to nanoceria using comet and chromosomal aberration (CA) assay and micronucleus test (MNT). It was concluded from the results that with high dose (1000 mg/kg BW) of nanoceria mediated DNA damage in liver cells and peripheral blood leukocytes (PBL). It further led to cytogenetic changes and micronucleus formation in bone cells and bone marrow [56].
In addition to this, another study consisted of the cytotoxic and genotoxic study of nanoceria in human neuroblastoma cell line (IMR 32). Nanoceria caused cytotoxicity which was confirmed by lactate dehydrogenase assays and 3-[4,5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide whereas genotoxicity assessment was confirmed using the cytokines-block micronucleus and comet assays. It was concluded that ROS were involved in the toxicity of nanoceria [57].
3.5. Neurotoxicity
Delivery of a targeted drug is a major concern and the most difficult job in neuroscience due to the fact that the blood-brain barrier (BBB) blocks most of the molecules and acts as a selective filter. In vitro and in vivo study confirmed that nanoparticles were used as carriers to move across the BBB i.e. the drug called suramin was used to cure the infection caused by the African trypanosomes which are the extracellular parasites. Presently, there is the availability of very few toxic drugs for this disease.
Therefore, the study was carried out to understand the responsive action of the brain that instructs the administration of suramin into the intracerebral region. Results have shown that the nanoceria which was fluorescently tagged when IV injected into mice induced nanoparticles accumulation in the liver and spleen. Moreover, very less penetration was seen in the brain.
Another in vitro and in vivo study elucidated neurotoxic effect caused due to nanoceria when exposed to serotonin (5-HT) which plays a vital role as a neurotransmitter. In vitro study of 5-HT demonstrated that nanoceria interacted with 5-HT and formed a 5-HT nanoceria complex. And in vitro study carried out in live zebrafish embryos depicted the lower level of 5-HT in the intestine due to prolonged exposure for more than 3 days. Therefore the exposure of 20 and 50 ppm nanoparticles decreased the 5-HT level to 20.5(±1.3) and 5.3(±1.5) nM respectively when exposed to 30.8 (±3.4) nM in control embryos (unexposed) [58].
4. Antioxidant activity
The most recent study described that when nanoceria was conjugated with levan, it depicted antioxidant activity. Levan coated nanoceria were synthesized using the system called one pot-and green synthesis. Levan acted as reducing and stabilizing agent. Moreover, there was a reduction in the level of ROS when levan coated nanoparticles were treated with hydrogen peroxide which stimulated NIH3T3 cells. Therefore, levan coated nanoparticles were beneficial towards the disease induced by ROS [59].
Another study has demonstrated that an average 10 nm size nanoceria extended the lifespan and preserved the neuronal function expressed in brain cell cultures. It was examined that the impact of Fe- doped nanoceria (6%Fe) was proved out to be less effective as compared to nanoceria.
The examination of 3 groups of nanoceria was done using H₂O₂, UV and Aβ₁₋₄ ₂ to find out the neuroprotective capacity. When compared to 7 nm nanoceria, the level of cell death decreased in 10 nm nanoceria which was induced by UV and H₂O₂. It was concluded that nanoceria depicted antioxidant activity and is size dependent. These nanoparticles protected the neurons from Aβ₁₋₄ ₂ toxicity and damage from free radicals [60].
4.1. In vitro study
In vitro studies are the evidence which proves nanoceria to be best antioxidants. They show ROS scavenging which protects different cells like stem [61], neuronal [62], [63], human breast [64], gastrointestinal epithelium [65] and endothelial [66]. Another study expressed that the drug doxorubicin had antitumor activity in human melanoma cells [67]. In A375 human melanoma cell line, cytotoxicity was seen and the cell viability decreased due to co-incubation of nanoceria and the drug doxorubicin. Anti-tumor activity and induced apoptosis were seen in A375 cell line but didn’t cause DNA damage.
In addition to this, researchers have reported that when PC12 neuron-like cells were incubated with an increase in the concentration of nanoceria, it was seen that PC12 cells depicted no deficiency in their metabolic activity and cell differentiation capabilities were retained. Moreover, there was an increase in neuronal length when cells were exposed to nanoceria. Further, there was a reduction in the production of ROS when stimulated with hydrogen peroxide. An increase in the production of dopamine was also seen [68].
Cytotoxicity assay of nanoceria was carried with human breast cancer (MCF-7) and fibrosarcoma (HT- 1080) cells. No cell death was seen when the cells were treated with 20 μg mL−1, 50 μg mL−1,100 μg mL−1 and 200 μg mL−1 concentration of nanoparticles. These nanoparticles treated cells lead to increase in the production of glutathione (GSH) and decrease the depletion of GSH caused due to hydrogen peroxide [69].
4.2. In vivo study
Many in vivo animal studies were carried out using rats and mice to understand the involvement of nanoceria in organs like liver, spleen, kidneys, lungs, and brain [70], [71], [72], [73], [74]. Another study reflected the absorption of ~ 30 nm in the liver and spleen via time and dose dependent manner [75]. And study was examined to understand the effects of 5 nm vs. 30 nm nanoceria in terms of size, shape and dose. But no difference was seen on the basis of retention and bio-distribution [76].
Very few studies were carried out with non-rodent models e.g. Drosophila melanogaster was chosen for in vivo study with nanoceria. It was confirmed that the uptake of nanoceria was seen in microvilli, interior parts of the intestine, intestinal lumen, hemolymph tissues and cytoplasm of intestinal cells. This was caused due to the ingestion of nanoceria as food, which passed through the intestine followed by the absorption in the mid-gut cells [77]. In addition to this, Caenorhabditis elegans was chosen as a model organism which was exposed to different charged surface coated nanoceria. It was observed that different surface coated nanoparticles had different uptake. Positively charged showed the best candidacy with highest bio-accumulation when compared to negative and neutral particles [78].
Several in vivo studies are carried out with plant crops like rice [79], wheat, sunflower, pumpkin [80], alfalfa, corn, tomato [81], kidney bean [82], radish [83], [84], cucumber [85], Rubia cordifolia [86] to study the uptake of nanoceria. Results have shown the highest uptake in roots as compared to other parts of plants like leaves shoots etc. [80], [81], [82], [83]. This is caused due to several factors like nanoceria size [80], [83], [85], agglomeration [85], [80] and concentration [81], [82] that lead to the uptake and distribution of nanoparticles.
5. Conclusion
The effect of nanoceria is a major concern among the researchers on the human health. We have discussed the overall processes and a recent synthesis of nanoceria via chemical and green methods. Synthesis using parts of plants extract is carried out for several years but we have included the most recent synthesis using flower extract that acts as chelating agent. Another recent chemical synthesis includes the preparation of nanoceria from a protein supra-molecule called apoferritin.
We have focused on the positive and negative impacts of nanoceria on different living organism model e.g. rat, mice, human cancer cell lines and non-rodent models. Controversy is seen in the study of nanoceria in the application of antioxidant property and toxicity analysis. However, mostly the studies focus on the toxicity of nanoceria on human health and different types of toxicity including cytotoxicity, genotoxicity, and neurotoxicity. We have exclusively focused on the antioxidant activities which are carried out both in vitro and in vivo. Many in vitro studies have concluded that nanoceria can be considered as safer nanoparticles as compared to the in vivo models.
We concluded that nanoceria was toxic towards human cancer cell lines. They can lead to the release of free radicals and oxidative stress ultimately leading to cell membrane damage and lipid peroxidation. However, ROS mediated DNA damage and cell cycle arrest. Finally, nanoceria can be used for several biomedical applications mostly for ROS related diseases like cardiac diseases, Alzheimer’s disease, and cancer. So, the ROS scavenging nanoceria can be considered as an alternative therapy for oxidative stress and several diseases and disorders.
References
- 1.Korsvik Cassandra. Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem. Commun. 2007;10:1056–1058. doi: 10.1039/b615134e. [DOI] [PubMed] [Google Scholar]
- 2.Dao Ngoc Nhiem. UV absorption by nanoceria/epoxy composite thin films. Adv. Nat. Sci.: Nanosci. Nanotechnol. 2011;2(4):045013. [Google Scholar]
- 3.Zholobak N.M. UV-shielding property, photocatalytic activity and photocytotoxicity of ceria colloid solutions. J. Photochem. Photobiol. B. 2011;102(1):32–38. doi: 10.1016/j.jphotobiol.2010.09.002. [DOI] [PubMed] [Google Scholar]
- 4.Alessandro Trovarelli. Alessandro Catalytic properties of ceria and CeO₂-containing materials. Catal. Rev. 1996;38(4):439–520. [Google Scholar]
- 5.Wang Ching-Huei, Lin Shiow-Shyung. Preparing an active cerium oxide catalyst for the catalytic incineration of aromatic hydrocarbons. Appl. Catal. A Gen. 2004;268(1):227–233. [Google Scholar]
- 6.Courbiere Blandine. Ultrastructural interactions and genotoxicity assay of cerium dioxide nanoparticles on mouse oocytes. Int. J. Mol. Sci. 2013;14(11):21613–21628. doi: 10.3390/ijms141121613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.De Marzi Laura. Cytotoxicity and genotoxicity of ceria nanoparticles on different cell lines in vitro. Int. J. Mol. Sci. 2013;14(2):3065–3077. doi: 10.3390/ijms14023065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Demokritou Philip. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO₂ inhalation exposures. Nanotoxicology. 2013;7(8):1338–1350. doi: 10.3109/17435390.2012.739665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Peng Lu. Comparative pulmonary toxicity of two ceria nanoparticles with the same primary size. Int. J. Mol. Sci. 2014;15(4):6072–6085. doi: 10.3390/ijms15046072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Pulido-Reyes Gerardo. Untangling the biological effects of nanoceria: the role of surface valence states. Sci. Rep. 2015;5:15613. doi: 10.1038/srep15613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Dahle Jessica T., Arai Yuji. Environmental geochemistry of cerium: applications and toxicology of nanoceria. Int. J. Environ. Res. Public Health. 2015;12(2):1253–1278. doi: 10.3390/ijerph120201253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Culcasi Marcel. EPR spin trapping evaluation of ROS production in human fibroblasts exposed to nanoceria: evidence for NADPH oxidase and mitochondrial stimulation. Chem. Biol. Interact. 2012;199(3):161–176. doi: 10.1016/j.cbi.2012.08.007. [DOI] [PubMed] [Google Scholar]
- 13.Perez J. Manuel. Synthesis of biocompatible dextran-coated nanoceria with pH-dependent antioxidant properties. Small. 2008;4(5):552–556. doi: 10.1002/smll.200700824. [DOI] [PubMed] [Google Scholar]
- 14.Urner Martin. Inflammatory response of lung macrophages and epithelial cells after exposure to redox active nanoparticles: effect of solubility and antioxidant treatment. Environ. Sci. Technol. 2014;48(23):13960–13968. doi: 10.1021/es504011m. [DOI] [PubMed] [Google Scholar]
- 15.Fisichella Matthieu. Toxicity evaluation of manufactured CeO₂ nanoparticles before and after alteration: combined physicochemical and whole-genome expression analysis in Caco-2 cells. BMC Genomics. 2014;15(1):700. doi: 10.1186/1471-2164-15-700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Leonardo Franchi P. Cyto-and genotoxic effects of metallic nanoparticles in untransformed human fibroblast. Toxicol. In Vitro. 2015;29(7):1319–1331. doi: 10.1016/j.tiv.2015.05.010. [DOI] [PubMed] [Google Scholar]
- 17.Pešić Milica. Anti-cancer effects of nanoceria and its intracellular redox activity. Chem. Biol. Interact. 2015;232:85–93. doi: 10.1016/j.cbi.2015.03.013. [DOI] [PubMed] [Google Scholar]
- 18.Lord Megan S. Cellular uptake and reactive oxygen species modulation of nanoceria in human monocyte cell line U937. Biomaterials. 2012;33(31):7915–7924. doi: 10.1016/j.biomaterials.2012.07.024. [DOI] [PubMed] [Google Scholar]
- 19.Rosenkranz P. Effects of nanoceria to fish and mammalian cell lines: an assessment of cytotoxicity and methodology. Toxicol. In Vitro. 2012;26(6):888–896. doi: 10.1016/j.tiv.2012.04.019. [DOI] [PubMed] [Google Scholar]
- 20.Xia Tian. Comparison of the mechanism of toxicity of zinc oxide and nanoceria based on dissolution and oxidative stress properties. ACS Nano. 2008;2(10):2121. doi: 10.1021/nn800511k. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Liu Y.H. Synthesis and character of cerium oxide (CeO₂) nanoparticles by the precipitation method. Metalurgija. 2014;53(4):463–465. [Google Scholar]
- 22.Zhang Qiu Li, Zhi Yang Mao, Ding Bing Jun. Synthesis of nanoceria by the precipitation method. Mater. Sci. Forum. 2009;vol. 610 Trans Tech Publications. [Google Scholar]
- 23.Kavitha P. Synthesis and characterization of nanoceria by using rapid precipitation method. PARIPEX-Indian J. Res. 2016;4(12) [Google Scholar]
- 24.Farahmandjou M., Zarinkamar M., Firoozabadi T.P. Synthesis of cerium oxide (CeO₂) nanoparticles using simple CO-precipitation method. Rev. Mex. Fis. 2016;62:496–499. [Google Scholar]
- 25.Babitha K.K. Structural characterization and optical studies of CeO₂ nanoparticles synthesized by chemical precipitation. Indian J. Pure Appl. Phys. (IJPAP) 2015;53(9):596–603. [Google Scholar]
- 26.Ketzial J., Jasmine A., Nesaraj S. Synthesis of CeO₂ nanoparticles by chemical precipitation and the effect of a sur-factant on the distribution of particle sizes. J. Ceram. Process. Res. 2011;12(1):74–79. [Google Scholar]
- 27.Shirke B.S. Synthesis of nanoceria by microwave technique using propylene glycol as a stabilizing agent. J. Mater. Sci. Mater. Electron. 2011;22(2):200–203. [Google Scholar]
- 28.Soren Siba. Antioxidant potential and toxicity study of the nanoceria synthesized by microwave-mediated synthesis. Appl. Biochem. Biotechnol. 2015;177(1):148–161. doi: 10.1007/s12010-015-1734-8. [DOI] [PubMed] [Google Scholar]
- 29.Pinjari Dipak Vitthal, Pandit Aniruddha Bhalchandra. Room temperature synthesis of crystalline CeO₂ nanopowder: advantage of sonochemical method over conventional method. Ultrason. Sonochem. 2011;18(5):1118–1123. doi: 10.1016/j.ultsonch.2011.01.008. [DOI] [PubMed] [Google Scholar]
- 30.Yin Lunxiang. Sonochemical synthesis of nanoceria—effect of additives and quantum size effect. J. Colloid Interface Sci. 2002;246(1):78–84. doi: 10.1006/jcis.2001.8047. [DOI] [PubMed] [Google Scholar]
- 31.Mutinda Samuel I. Dissertations. Youngstown State University; 2013. Hydrothermal synthesis of shape/size-controlled cerium-based oxides. [Google Scholar]
- 32.Kepenekci Özlem. MS Thesis. İzmir Institute of Technology; 2009. Hydrothermal preparation of single crystalline CeO₂ nanoparticles and the influence of alkali hydroxides on their structure and optical behavior. [Google Scholar]
- 33.Masui T. Synthesis of nanoceria by hydrothermal crystallization with citric acid. J. Mater. Sci. Lett. 2002;21(6):489–491. [Google Scholar]
- 34.Masui Toshiyuki. Synthesis and characterization of nanoceria coated with turbostratic boron nitride. J. Mater. Chem. 2003;13(3):622–627. [Google Scholar]
- 35.Jalilpour Marzieh, Fathalilou Mohammad. Effect of aging time and calcination temperature on the nanoceria synthesis via reverse co-precipitation method. Int. J. Phys. Sci. 2012;7(6):944–948. [Google Scholar]
- 36.Gao Feng, Lu Qingyi, Komarneni Sridhar. Fast synthesis of nanoceria and nanorods. J. Nanosci. Nanotechnol. 2006;6(12):3812–3819. doi: 10.1166/jnn.2006.609. [DOI] [PubMed] [Google Scholar]
- 37.Okuda Mitsuhiro, Suzumoto Yoko, Yamashita Ichiro. Bioinspired synthesis of homogenous nanoceria and two-or three-dimensional nanoparticle arrays using protein supramolecules. Cryst. Growth Des. 2011;11(6):2540–2545. [Google Scholar]
- 38.Arumugam Ayyakannu. Synthesis of nanoceria using Gloriosa superba L. leaf extract and their structural, optical and antibacterial properties. Mater. Sci. Eng. C. 2015;49:408–415. doi: 10.1016/j.msec.2015.01.042. [DOI] [PubMed] [Google Scholar]
- 39.Munusamy S., Bhakyaraj K., Vijayalakshmi L., Stephen A., Narayanan V. Synthesis and characterization of nanoceria using Curvularia lunata and their antibacterial properties. Int. J. Innov. Res. Sci. Eng. 2014;2(1):318–323. [Google Scholar]
- 40.Maqbool Q., Nazar M., Naz S. Antimicrobial potential of green synthesized CeO2 nanoparticles from Olea europaea leaf extract. Int. J. Nanomed. 2016;11:5015–5025. doi: 10.2147/IJN.S113508. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Kannan S.K., Sundrarajan M. A green approach for the synthesis of a cerium oxide nanoparticle: characterization and antibacterial activity. Int. J. Nanosci. 2014;13(03):1450018. [Google Scholar]
- 42.Priya G.S., Kanneganti A., Kumar K.A., Rao K.V., Bykkam S. Bio synthesis of nanoceria using Aloe arbadensis Miller Gel. Int. J. Sci. Res. Publ. 2014;4(6):1–4. [Google Scholar]
- 43.Thovhogi N., Diallo A., Gurib-Fakim A., Maaza M. Nanoparticles green synthesis by Hibiscus Sabdariffa flower extract: main physical properties. J. Alloys Compd. 2015;647:392–396. [Google Scholar]
- 44.Kargar H., Ghazavi H., Darroudi M. Size-controlled and bio-directed synthesis of ceria nanopowders and their in vitro cytotoxicity effects. Ceramics Int. 2015;41(3):4123–4128. [Google Scholar]
- 45.Singh A.V., Bandgar B.M., Kasture M., Prasad B.L.V., Sastry M. Synthesis of gold, silver and their alloy nanoparticles using bovine serum albumin as foaming and stabilizing agent. J. Mater. Chem. 2005;15(48):5115–5121. [Google Scholar]
- 46.Darroudi M., Hoseini S.J., Kazemi Oskuee R., Hosseini H.A., Gholami L., Gerayli S. Food-directed synthesis of nanoceria and their neurotoxicity effects. Ceramics Int. 2014;40(5):7425–7430. [Google Scholar]
- 47.Ravishankar Thammadihalli Nanjundaiah. Synthesis and characterization of CeO₂ nanoparticles via solution combustion method for photocatalytic and antibacterial activity studies. ChemistryOpen. 2015;4(2):146–154. doi: 10.1002/open.201402046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Dos S., Carlos C.L. Antimicrobial activity of nano cerium oxide (IV)(CeO₂) against Streptococcus mutans. BMC Proceedings. 2014;8(4) [Google Scholar]
- 49.Limbach L.K. Oxide nanoparticle uptake in human lung fibroblasts: effects of particle size, agglomeration, and diffusion at low concentrations. Environ. Sci. Technol. 2005;39:9370–9376. doi: 10.1021/es051043o. [DOI] [PubMed] [Google Scholar]
- 50.Rzigalinski B. Nanoparticles and cell longevity. Technol. Cancer Res. Treat. 2005;4(6):651–659. doi: 10.1177/153303460500400609. [DOI] [PubMed] [Google Scholar]
- 51.Limbach L.K. Removal of oxide nanoparticles in a model wastewater treatment plant: influence of agglomeration and surfactants on clearing efficiency. Environ. Sci. Technol. 2008;42(15):5828–5833. doi: 10.1021/es800091f. [DOI] [PubMed] [Google Scholar]
- 52.Lin Weisheng. Toxicity of nanoceria in human lung cancer cells. Int. J. Toxicol. 2006;25(6):451–457. doi: 10.1080/10915810600959543. [DOI] [PubMed] [Google Scholar]
- 53.Renu G. Development of nanoceria and its cytotoxicity in prostate cancer cells. Adv. Sci. Lett. 2012;6(1):17–25. [Google Scholar]
- 54.Prasad, k. Wallace R.Y., Tennant H., k. Kitchin T., Kligerman D., Blackman C.F. Presented at Genetics & Environmental Mutagenesis Society; Chapel Hill, NC: 2009. The Genotoxicity of Titanium Dioxide and Nanoceria in Vitro. [Google Scholar]
- 55.Mittal Sandeep, Alok Pandey K. Nanoceria induced toxicity in human lung cells: role of ROS mediated DNA damage and apoptosis. BioMed Res. Int. 2014 doi: 10.1155/2014/891934. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Kumari Monika. Genotoxicity assessment of nanoceria in female Wistar rats after acute oral exposure. Mutat. Res./Genet. Toxicol. Environ. Mutagen. 2014;775:7–19. doi: 10.1016/j.mrgentox.2014.09.009. [DOI] [PubMed] [Google Scholar]
- 57.Kumari Monika. Toxicity study of nanoceria in human neuroblastoma cells. Int. J. Toxicol. 2014;33(2):86–97. doi: 10.1177/1091581814522305. [DOI] [PubMed] [Google Scholar]
- 58.Özel Rıfat Emrah. Effect of nanoceria on intestinal serotonin in zebrafish. RSC Adv. 2013;3(35):15298–15309. doi: 10.1039/C3RA41739E. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59.Kim Sun-Jung, Chung Bong Hyun. Antioxidant activity of levan coated nanoceria. Carbohydr. Polym. 2016;150:400–407. doi: 10.1016/j.carbpol.2016.05.021. [DOI] [PubMed] [Google Scholar]
- 60.Singh Neeraj. The antioxidant activity of nanoceria is size dependant and blocks Aβ1-42-induced free radical production and neurotoxicity. FASEB J. 2008;22(1) (624-2) [Google Scholar]
- 61.Mandoli Corrado. Stem cell aligned growth induced by CeO₂ nanoparticles in PLGA scaffolds with improved bioactivity for regenerative medicine. Adv. Funct. Mater. 1617-1624;20(10):2010. [Google Scholar]
- 62.Pagliari Francesca. Nanoceria protect cardiac progenitor cells from oxidative stress. ACS Nano. 2012;6(5):3767–3775. doi: 10.1021/nn2048069. [DOI] [PubMed] [Google Scholar]
- 63.Schubert David. Cerium and yttrium oxide nanoparticles are neuroprotective. Biochem. Biophys. Res. Commun. 2006;342(1):86–91. doi: 10.1016/j.bbrc.2006.01.129. [DOI] [PubMed] [Google Scholar]
- 64.Tarnuzzer Roy W. Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett. 2005;5(12):2573–2577. doi: 10.1021/nl052024f. [DOI] [PubMed] [Google Scholar]
- 65.Colon Jimmie. Nanoceria protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomed. Nanotechnol. Biol. Med. 2010;6(5):698–705. doi: 10.1016/j.nano.2010.01.010. [DOI] [PubMed] [Google Scholar]
- 66.Chen Shizhu. Nanoceria protect endothelial cells from apoptosis induced by oxidative stress. Biol. Trace Elem. Res. 2013;154(1):156–166. doi: 10.1007/s12011-013-9678-8. [DOI] [PubMed] [Google Scholar]
- 67.Sack Maren. Combination of conventional chemotherapeutics with redox-active nanoceria—A novel aspect in cancer therapy. Mol. Cancer Ther. 2014;13(7):1740–1749. doi: 10.1158/1535-7163.MCT-13-0950. [DOI] [PubMed] [Google Scholar]
- 68.Ciofani Gianni. Effects of nanoceria on PC12 neuronal-like cells: proliferation, differentiation, and dopamine secretion. Pharm. Res. 2013;30(8):2133–2145. doi: 10.1007/s11095-013-1071-y. [DOI] [PubMed] [Google Scholar]
- 69.Akhtar Mohd Javed. Glutathione replenishing potential of CeO₂ nanoparticles in human breast and fibrosarcoma cells. J. Colloid Interface Sci. 2015;453:21–27. doi: 10.1016/j.jcis.2015.04.049. [DOI] [PubMed] [Google Scholar]
- 70.Hardas Sarita S. Brain distribution and toxicological evaluation of a systemically delivered engineered nanoscale ceria. Toxicol. Sci. 2010:137. doi: 10.1093/toxsci/kfq137. [DOI] [PubMed] [Google Scholar]
- 71.Dan Mo. Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial. Int. J. Nanomed. 2012;7:4023. doi: 10.2147/IJN.S32526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72.Rojas Santiago. In vivo biodistribution of amino-functionalized ceria nanoparticles in rats using positron emission tomography. Mol. Pharm. 2012;9(12):3543–3550. doi: 10.1021/mp300382n. [DOI] [PubMed] [Google Scholar]
- 73.Portioli Corinne. Short-term biodistribution of nanoceria in mice: focus on brain parenchyma. Nanosci. Nanotechnol. Lett. 2013;5(11):1174–1181. [Google Scholar]
- 74.Yang Likun. Intrinsically radiolabeled multifunctional nanoceria for in vivo studies. J. Mater. Chem. B. 2013;1(10):1421–1431. doi: 10.1039/c2tb00404f. [DOI] [PubMed] [Google Scholar]
- 75.Yokel Robert A. Biodistribution and oxidative stress effects of a systemically-introduced commercial ceria engineered nanomaterial. Nanotoxicology. 2009;3(3):234–248. [Google Scholar]
- 76.Yokel Robert A. Nanoceria biodistribution and retention in the rat after its intravenous administration are not greatly influenced by dosing schedule, dose, or particle shape. Environ. Sci. Nano. 2014;1(6):549–560. [Google Scholar]
- 77.Alaraby Mohamed. Antioxidant and antigenotoxic properties of CeO₂ NPs and cerium sulphate: studies with Drosophila melanogaster as a promising in vivo model. Nanotoxicology. 2015;9(6):749–759. doi: 10.3109/17435390.2014.976284. [DOI] [PubMed] [Google Scholar]
- 78.Collin Blanche. Influence of natural organic matter and surface charge on the toxicity and bioaccumulation of functionalized ceria nanoparticles in Caenorhabditis elegans. Environ. Sci. Techno. 2014;48(2):1280–1289. doi: 10.1021/es404503c. [DOI] [PubMed] [Google Scholar]
- 79.Rico Cyren M. Effect of nanoceria on rice: a study involving the antioxidant defense system and in vivo fluorescence imaging. Environ. Sci. Technol. 2013;47(11):5635–5642. doi: 10.1021/es401032m. [DOI] [PubMed] [Google Scholar]
- 80.Schwabe Franziska. Dissolved cerium contributes to uptake of Ce in the presence of differently sized CeO₂-nanoparticles by three crop plants. Metallomics. 2015;7(3):466–477. doi: 10.1039/c4mt00343h. [DOI] [PubMed] [Google Scholar]
- 81.López-Moreno Martha L. X-ray absorption spectroscopy (XAS) corroboration of the uptake and storage of CeO₂ nanoparticles and assessment of their differential toxicity in four edible plant species. J. Agric. Food Chem. 2010;58(6):3689–3693. doi: 10.1021/jf904472e. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82.Majumdar Sanghamitra. Environmental effects of nanoceria on seed production of common bean (Phaseolus vulgaris): a proteomic analysis. Environ. Sci. Technol. 2015;49(22):13283–13293. doi: 10.1021/acs.est.5b03452. [DOI] [PubMed] [Google Scholar]
- 83.Zhang Weilan. Uptake and accumulation of bulk and nanosized cerium oxide particles and ionic cerium by radish (Raphanus sativus L.) J. Agric. Food Chem. 2015;63(2):382–390. doi: 10.1021/jf5052442. [DOI] [PubMed] [Google Scholar]
- 84.Trujillo-Reyes J. Citric acid modifies surface properties of commercial CeO₂ nanoparticles reducing their toxicity and cerium uptake in radish (Raphanus sativus) seedlings. J. Hazard. Mater. 2013;263:677–684. doi: 10.1016/j.jhazmat.2013.10.030. [DOI] [PubMed] [Google Scholar]
- 85.Zhang Zhiyong. Uptake and distribution of ceria nanoparticles in cucumber plants. Metallomics. 2011;3(8):816–822. doi: 10.1039/c1mt00049g. [DOI] [PubMed] [Google Scholar]
- 86.Sisubalan N., Ramkumar V.S., Pugazhendhi A., Karthikeyan C., Indira K., Gopinath K., Hameed A.S.H. Basha MHG.ROS-mediated cytotoxic activity of ZnO and CeO2 nanoparticles synthesized using the Rubia cordifolia L. leaf extract on MG-63 human osteosarcoma cell lines. Environ. Sci. Pollut. Res. 2017:1–11. doi: 10.1007/s11356-017-0003-5. [DOI] [PubMed] [Google Scholar]