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Nanoceria - SOD mimetic, antioxidant, autophagy, anti-cancer

nanoceria autophagy antioxidant cerium

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#1 Kalliste

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Posted 08 April 2015 - 10:43 AM

 I can't believe nobody is self-experimenting with this stuff, it seems great. I have recently been noticing this substance when browsing antioxidant papers.


Has anyone tried this as a supplement? It seems a bit reminiscent of fullerenes in some sense.






Cerium oxide nanoparticles (nanoceria) have recently been shown to protect cells against oxidative stress in both cell culture and animal models. Nanoceria has been shown to exhibit superoxide dismutase (SOD) activity using a ferricytochrome C assay, and this mimetic activity that has been postulated to be responsible for cellular protection by nanoceria. The nature of nanoceria's antioxidant properties, specifically what physical characteristics make nanoceria effective at scavenging superoxide anion, is poorly understood. In this study electron paramagnetic resonance (EPR) analysis confirms the reactivity of nanoceria as an SOD mimetic. X-ray photoelectron spectroscopy (XPS) and UV–visible analyses of nanoceria treated with hydrogen peroxide demonstrate that a decrease in the Ce 3+/4+ ratio correlates directly with a loss of SOD mimetic activity. These results strongly suggest that the surface oxidation state of nanoceria plays an integral role in the SOD mimetic activity of nanoceria and that ability of nanoceria to scavenge superoxide is directly related to cerium(III) concentrations at the surface of the particle.



The therapeutic application of nanomaterials has been a focus of numerous studies in the past decade. Due to its unique redox properties, cerium oxide (ceria) is finding widespread use in the treatment of medical disorders caused by the reactive oxygen intermediates (ROI). The radical-scavenging role of ceria nanoparticles (nanoceria) have been established, as well as the autocatalytic ability of nanoceria to regenerate under various environmental conditions. The synthesis of nanoceria in biocompatible media has also been reported along with cell viability in order to determine the potential use of nanoceria in biomedical applications.



In this study we have found that cerium oxidenanoparticles exhibit catalase mimetic activity. Surprisingly, the catalase mimetic activity correlates with a reduced level of cerium in the +3 state, in contrast to the relationship between surface charge and superoxide scavenging properties.





Ovarian cancer (OvCa) is the fifth most common cause of death from all cancers among women in United Sates and the leading cause of death from gynecological malignancies. While most OvCa patients initially respond to surgical debulking and chemotherapy, 75% of patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with OvCa. In this context, we have developed and engineered Nanoceria (NCe), nanoparticles of cerium oxide, possessing anti-oxidant properties, to be used as a therapeutic agent in OvCa. We show for the first time that NCe significantly inhibited production of reactive oxygen species (ROS) in A2780 cells, attenuated growth factor (SDF1, HB-EGF, VEGF165 and HGF) mediated cell migration and invasion of SKOV3 cells, without affecting the cell proliferation. NCe treatment also inhibited VEGF165 induced proliferation, capillary tube formation, activation of VEGFR2 and MMP2 in human umbilical vascular endothelial cells (HUVEC). NCe (0.1 mg/kg body weigh) treatment of A2780 ovarian cancer cells injected intra-peritoneally in nude mice showed significant reduction (p<0.002) in tumor growth accompanied by decreased tumor cell proliferation as evident from reduced tumor size and Ki67 staining. Accumulation of NCe was found in tumors isolated from treated group using transmission electron microscopy (TEM) and inductively coupled plasma mass spectroscopy (ICP-MS). Reduction of the tumor mass was accompanied by attenuation of angiogenesis, as observed by reduced CD31 staining and specific apoptosis of vascular endothelial cells. Collectively, these results indicate that cerium oxide based NCe is a novel nanoparticle that can potentially be used as an anti-angiogenic therapeutic agent in ovarian cancer.





Tissue engineering and regenerative medicine aim to achieve functional restoration of tissue or cells damaged through disease, aging, or trauma. Advancement of tissue engineering requires innovation in the field of three-dimensional scaffolding and functionalization with bioactive molecules. Nanotechnology offers advanced materials with patterned nano-morphologies for cell growth and different molecular substrates that can support cell survival and functions. Cerium oxide nanoparticles (nanoceria) can control intracellular as well as extracellular reactive oxygen and nitrogen species. Recent findings suggest that nanoceria can enhance long-term cell survival, enable cell migration and proliferation, and promote stem cell differentiation. Moreover, the self-regenerative property of nanoceria permits a small dose to remain catalytically active for an extended time. This review summarizes the possibilities and applications of nanoceria in the field of tissue engineering and regenerative medicine.



Autophagy is one of the cellular housekeeping processes responsible for promptly clearing out damaged proteins and cell components before they cause more harm. Autophagic activity declines with age, in part due to a build up of resilient metabolic waste in lysosomes, the organelles responsible for breaking down materials and structures for recycling. The SENS strategy for this contribution to degenerative aging is to aim to remove that waste in order to restore function. Globally increased autophagy is also a factor in many genetic and other alterations shown to slow aging and increase healthy life span in laboratory animals. Thus some researchers are investigating ways to boost this form of cellular housekeeping, and there have been some interesting demonstrations over the years, such as restoration of youthful liver function in old mice. Here one research group finds that nanoparticles can spur greater autophagy:

Cerium oxide nanoparticles (nanoceria) are widely used in a variety of industrial applications including UV filters and catalysts. The expanding commercial scale production and use of ceria nanoparticles have inevitably increased the risk of release of nanoceria into the environment as well as the risk of human exposure. The use of nanoceria in biomedical applications is also being currently investigated because of its recently characterized antioxidative properties. In this study, we investigated the impact of ceria nanoparticles on the lysosome-autophagy system, the main catabolic pathway that is activated in mammalian cells upon internalization of exogenous material.

We tested a battery of ceria nanoparticles functionalized with different types of biocompatible coatings expected to have minimal effect on lysosomal integrity and function. We found that ceria nanoparticles promote activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and induce upregulation of genes of the lysosome-autophagy system. We further show that the array of differently functionalized ceria nanoparticles tested in this study enhance autophagic clearance of proteolipid aggregates that accumulate as a result of inefficient function of the lysosome-autophagy system.

This study provides a mechanistic understanding of the interaction of ceria nanoparticles with the lysosome-autophagy system and demonstrates that ceria nanoparticles are activators of autophagy and promote clearance of autophagic cargo. These results provide insights for the use of nanoceria in biomedical applications, including drug delivery. These findings will also inform the design of engineered nanoparticles with safe and precisely controlled impact on the environment and the design of nanotherapeutics for the treatment of diseases with defective autophagic function and accumulation of lysosomal storage material.

Link: http://dx.doi.org/10.1021/nn505073u





We report the direct synthesis of cerium oxide nanoparticles (CNPs) in polyethylene glycol (PEG) based solutions with efficient radical scavenging properties. Synthesis of CNPs in PEG demonstrated a concentration dependent (of PEG) redox activity characterized by UV−visible spectroscopy. PEGylated CNPs acted as efficient radical scavengers, and superoxide dismutase (SOD) activity of CNPs synthesized in various concentration of PEG did not reduce compared to bare nanoceria. In addition to superoxide, PEGylated nanoceria demonstrated quenching of peroxide radicals as well. It was observed that the reaction with hydrogen peroxide leads to the formation of a charge transfer complex governed by the concentration of PEG. The stability of the charge transfer complex provides the tunable oxidation state of CNPs. The stability of this complex influences the regenerative capacity of the active 3+ oxidation state of CNPs. The cell viability as well as SOD activity of PEGylated CNPs is compared to those of bare CNPs, and the differences are outlined.


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#2 Kalliste

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Posted 16 April 2015 - 08:56 AM

Heres another study with what I think is very large doses of nanoceria, of some sort. I don't think this has been functionalized. I will reread later when I have more time. They did cause some inflammation but they did not seem to be very toxic at all, which is good for someone who wants to experiment :)



4. Conclusions

Acute and subacute toxicity assays demonstrate no lethal effect of the ceria NPs but it is not correct to assert that CeO2 NPs are totally harmless for living systems as they can induce inflammation in various organs, as revealed by TEM and histological analysis and hematological parameters evaluation. TEM analysis revealed the presence of NPs into liver and alveolar macrophages, generating a localized inflammation status. The optical evaluation confirmed the ceria NPs presence in these two organs and their presence can be explained with the ability of these NPs to enter the blood stream and lately reach specific organs. The inflammation status is confirmed by the chemical-clinical evaluations that revealed a variation in the hematological and plasmatic values (ALT, AST, and total bilirubin) as well as kidney functionality (creatinine). So it can be hypothesized an inflammation situation in these organs (in mice so possibly even in humans), based on lymphoid cells agglomeration in those organs, especially close to liver blood vessels and in the cortical kidney portion; even the Peyer's plaque dimensions can sustain the hypotheses of an immune system variation, as they appear to be larger and bigger in the treated animals than in control mice group. Anyhow, the dose-response relationship is not linear as, at the high concentration tested, the biological parameter results more similar to the negative control group than the low and media dose group. This trend was evident even in the subacute test so an explanation needed to be found; considering the subacute test, the leukocyte formula trend revealed and confirmed the inflammation processes, in this case without any correlation between the concentration used and the toxic effect found. A possible explanation can be that the high dose tested is so high that NPs aggregate without passing through the detoxification organs (as kidney and/or liver) and without laying into them, avoiding the trigger of inflammation processes. In this case, only a small amount of NPs is free to pass into the detoxification organs and generate the low degrees of inflammation as well as the low variation in the leukocyte formula (especially the neutrophil line, confirming the initial status of the inflammation). Summarizing the in vivo murine assays, CeO2 NPs resulted to be neither cytotoxic nor genotoxic but they proved to be able to be uptaken by liver and to reach lungs by hematic flux.


Edited by Cosmicalstorm, 16 April 2015 - 08:57 AM.

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#3 Kalliste

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Posted 07 May 2015 - 06:51 AM

Here is some more. 3.8nm seems to be the really good stuff :)



Antioxidant Properties of Cerium Oxide Nanocrystals as a Function of Nanocrystal Diameter and Surface Coating

Department of Chemistry, Rice University, Houston, Texas 77005, United States
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005, United States
ACS Nano, 2013, 7 (11), pp 9693–9703
DOI: 10.1021/nn4026806
Publication Date (Web): September 30, 2013
Copyright © 2013 American Chemical Society
*Address correspondence to colvin@rice.edu.

This work examines the effect of nanocrystal diameter and surface coating on the reactivity of cerium oxide nanocrystals with H2O2 both in chemical solutions and in cells. Monodisperse nanocrystals were formed in organic solvents from the decomposition of cerium precursors, and subsequently phase transferred into water using amphiphiles as nanoparticle coatings. Quantitative analysis of the antioxidant capacity of CeO2–x using gas chromatography and a luminol test revealed that 2 mol of H2O2 reacted with every mole of cerium(III), suggesting that the reaction proceeds via a Fenton-type mechanism. Smaller diameter nanocrystals containing more cerium(III) were found to be more reactive toward H2O2. Additionally, the presence of a surface coating did not preclude the reaction between the nanocrystal surface cerium(III) and hydrogen peroxide. Taken together, the most reactive nanoparticles were the smallest (e.g., 3.8 nm diameter) with the thinnest surface coating (e.g., oleic acid). Moreover, a benchmark test of their antioxidant capacity revealed these materials were 9 times more reactive than commercial antioxidants such as Trolox. A unique feature of these antioxidant nanocrystals is that they can be applied multiple times: over weeks, cerium(IV) rich particles slowly return to their starting cerium(III) content. In nearly all cases, the particles remain colloidally stable (e.g., nonaggregated) and could be applied multiple times as antioxidants. These chemical properties were also observed in cell culture, where the materials were able to reduce oxidative stress in human dermal fibroblasts exposed to H2O2 with efficiency comparable to their solution phase reactivity. These data suggest that organic coatings on cerium oxide nanocrystals do not limit the antioxidant behavior of the nanocrystals, and that their redox cycling behavior can be preserved even when stabilized.


#4 Kalliste

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Posted 07 May 2015 - 08:01 AM

This substance reminds me a terrible lot of C60OO and IAC in the sense that it seems to be an autocatalytic antioxidant with high bioavailability. Seems to be low-tox under right circumstances. I'm tempted to see if I can find some 3.8nm and mix it with olive oil :)

#5 Kalliste

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Posted 07 May 2015 - 08:10 AM

Novel synthesis of cerium oxide nanoparticles for free radical scavenging

Yi-Yang Tsai​‌1, Jose Oca-Cossio​‌2, Kristina Agering​‌2, Nicholas E Simpson​‌2, Mark A Atkinson​‌3, Clive H Wasserfall​‌3, Ioannis Constantinidis​‌2 & Wolfgang Sigmund​‌1

† Author for correspondence



Aims: The aim of this article is to present a novel synthetic route to form CeO2 nanoparticles that protects against the detrimental influence of oxidative stress in mammalian cells. Methods: The noncytotoxic surfactant lecithin was used to synthesize CeO2 nanoparticles and the products were colloidally stabilized in a biocompatible tri-sodium citrate buffer. These nanoparticles were delivered into murine insulinoma βTC-tet cells, and intracellular free radical concentrations responding to exposure to hydroquinone were measured in a variety of extracellular CeO2 concentrations. Results: Well-dispersed, highly crystallized CeO2 nanoparticles of 3.7 nm in size were achieved that are chemically and colloidally stable in Dulbecco’s modified Eagle’s medium for extended periods of time. Treating βTC-tet cells with these nanoparticles alleviated detrimental intracellular free radical levels down to the primary level. Conclusion: CeO2 nanoparticles synthesized from this route are demonstrated to be effective free radical scavengers within βTC-tet cells. Furthermore, it is shown that CeO2 nanoparticles provide an effective means to improve cellular survival in settings wherein cell loss due to oxidative stress limits native function.




#6 Kalliste

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Posted 07 May 2015 - 10:20 AM


Cerium oxide nanoparticles (nanoceria, NC) are considered

an ideal inorganic antioxidant, owing to their self–regenerative

capability of free radical scavengers (1). These nanoparticles

in fact show interesting redox activity because of the

presence of crystalline defects on their surface, that allow for

the presence of both Ce4+ and Ce3+ species (2).

Many studies confirmed that, in biological contexts,

nanoceria exhibit antioxidant effects, owing both superoxide

dismutase (3–5) and catalase (6) mimetic activities. Recently,

our group showed that the reactive oxygen species (ROS)

scavenging property of nanoceria positively affects neuronal

differentiation and dopamine production in PC12 cells (7, 8).

Moreover, nanoceria have been widely investigated for the

treatment of several disorders, including cardiomyopathy (9),

cancer (10), and in the treatment of injuries of the spinal cord

(11). To date, several antioxidant therapies were developed to

reduce the ROS production involved in the pathogenesis of

various diseases; however, traditional antioxidant agents like

vitamins (12), nitrones (13) and exogenous superoxide

dismutases (SODs) (14) suffer of some limitations ranging from

enzymatic degradation, to the difficulty to reach the target,

and to their short half-life. It is therefore clear that the growing

interest on nanoceria is due to their antioxidant autoregenerative

ability (15).

One of the proposed models that explain this activity

suggests that Ce3+ reduce superoxide forming H2O2 and

Ce4+, while H2O2 and Ce4+ restore Ce3+ and develop O2

(16). The NC auto-regenerating antioxidant activity made

them thus suitable to finely control ROS levels in cells, tissues,

and, ultimately, organisms (17). ROS are in fact generally

associated with negative effects, because oxidative damages

to proteins and nucleic acids are often at the base of important

pathologies like cancer and neurodegenerative diseases (18).

However, in some cases, ROS may have many physiological

roles, including signaling and control of inflammatory

response and cell proliferation (19), thus their tuning through

NC administration has to be carefully evaluated.

Among different pathological conditions, several studies

have pointed out a correlation between oxidative stress and

adiposity (20–22). The mechanisms through which ROS promote

adipocytematuration are still not completely clear, but it

has been demonstrated that mitotic clonal expansion during

adipocyte differentiation is accelerated by oxidant treatment

(23). A study reported that the link between fat accumulation

and ROS is the protein PKCβ, which, once activated by

oxidative species, induces the adipogenic process (24).

Excessive fat accumulation (25), better known as obesity,

affects 11% of the world population (data fromWorld Health

Organization statistics, 2008). Obesity is often associated with

several metabolic disorders (diabetes, hypertension, etc.), commonly

defined together as “metabolic syndrome”, that increase

the risk of mortality (26). In the recent years, many

methods have been approached to reduce fat accumulation in

obese patients, such as physical activity, diet, surgery, and

pharmacotherapies (27). However, sometimes lifestyle

modification and pharmacologic treatment are not enough

to achieve a significant weight loss (28).

In this study, we investigated the effects of the antioxidant

activity of nanoceria in reducing the capability to differentiate

into adipocytes of mesenchymal stem cells, used as model of

adypogenesis (29): our purpose is to demonstrate the inhibition

of adipogenesis induced by nanoceria in order to exploit

these nanoparticles in potential therapeutic treatments of






In vitro studies proved that nanoceria exhibit two complementary

behaviors: while they generally have antioxidant effects

prolonging the cell survival, on the other hand, at acidic pH

values, they act as an oxidase, thus generating ROS (30). In

this study, the antioxidant property of NC was examined as a

potential agent of inhibition of adipogenesis in MSCs. It is in

fact well established that MSCs are precursor of adipocytes,

and they are an excellent model for the study of innovative

therapies in the treatment of adiposity (31).

First of all, we confirmed the cytocompatibility of NC on

MSCs. Other studies demonstrated that NC are not toxic for

various cell lines (32–34), and even in the case of MSCs, NC

up to 100 μg/ml do not present negative effects on the cells in

terms of viability, proliferation, and cytoskeletal

conformation. Thereafter, we assessed the interaction

of NC with MSCs, revealing a strong membrane association

(with SEM analysis) and internalization (with

confocal microscopy) with a preferential distribution at

the cytoplasm level, without co-localization in acidic

compartments of the cells. NC are not distributed in

mitochondria as instead reported by Singh et al. for

keratinocytes (35); moreover, the absence of NC in the

lysosomes avoids its pro-oxidant effects at acidic pH


The evaluation of the gene expression of the differentiating

samples treated with NC for 14 days demonstrated a significant

decrement of the main adipogenesis marker genes with

respect to the control. The examined genes for the induction

of the adipogenic differentiation were Pparg, Cebpa, Lpl and

Gpd1. Peroxisome proliferator-activated receptor gamma

(coded by Pparg) is the key transcription factor that induces

adipocyte differentiation (37), and its product induces the

expression of the gene CAAT/enhancer-binding protein alpha

(Cebpa), by binding its promoter. Together, Pparg and

Cebpa activate several genes that are involved in the development

of adipocytes, like lipoprotein lipase (coded by Lpl) and

glycerol-3-phosphate dehydrogenase (coded by Gpd1) (38). In

particular, the lipoprotein lipase has the function of hydrolyzing

triglycerides in the early stage of adipogenesis (39), while

glycerol-3-phosphate dehydrogenase is involved in the biosynthesis

of lipids at the end of the adipocyte maturation (40).

Inhibitory effects of NC on adipogenesis were confirmed

by the phenotype analysis of the cultures, both in terms of

lipidic vesicles quantification and of G3PDH activity. This

enzyme, in particular, catalyzes the conversion of glycerol-3-

phosphate into dihydroxyacetone phosphate in the mitochondrial

membrane (41). In cells treated with NC, the activity of

G3PDH strongly decreased with respect to the control.

Taken together, these data suggest that the presence of NC

inhibits the development of mature adipocytes (42). The

mechanism of this effect is likely related to a ROS level

reduction induced by the NC, that thus hinder a complete

maturation of adipocytes. As widely recognized, NC in fact

are able to reduce intracellular oxidative stress in several

biological contexts (43–45). Plenty of researches delineate

the involvement of the reactive oxygen species in the promotion

of stem cell differentiation into mature adipocytes

(46–48); as Supplementary Material we have reported ROS

evaluation in proliferatingMSCs and in differentiatingMSCs,

treated with NC and with N-acetyl-L-cysteine as anti-oxidant

positive control, confirming high ROS production after adipogenesis

induction, and its strong reduction when NC are

provided to the cells. The correlation between redox mechanism

and adipogenesis was moreover proved by Kanda et al.,

that identified cAMP response element-binding protein 1

(Creb1) as the transcription factor activated by ROS in

MSCs (49). Creb1 is necessary to induce adipogenesis as it is

involved in the transcriptional activation of Pparg (50). Hence,

we hypothesized a possible pathway in which NC scavenge

ROS, thus reducing the transcription of Creb1 as confirmed by

our qRT-PCR results (Fig. 8(a)), eventually hindering downstream

activations that would lead to a complete adipocyte

maturation (Fig. 8(b)).


In this study, we reported the behavior of MSCs differentiating

toward adipocytes in the presence of NC, in terms of

cytotoxic effects and adipogenic maturation. At the end of

the experimental analysis, a clear decrement of adipogenesis

was highlighted in cultures treated with NC at concentrations

that do not affect their viability/proliferation. This effect,

ascribable to the anti-oxidant properties of NC that scavenge

the ROS necessary for a correct adipogenesis, represents an

encouraging step toward NC-based therapy against obesity

and other related metabolic syndromes.


#7 Kalliste

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Posted 07 May 2015 - 10:55 AM

Added to diesel it seems to protect the brain of the rats who inhaled it.




One of the uses of cerium oxide nanoparticles (nanoceria, CeO2) is as a diesel fuel additive to improve fuel efficiency. Gene/environment interactions are important determinants in the etiology of age-related disorders. Thus, it is possible that individuals on high-fat diet and genetic predisposition to vascular disease may be more vulnerable to the adverse health effects of particle exposure. The aim of this pilot study was to test the hypothesis that inhalation of diesel exhaust (DE) or diesel exhaust-containing cerium oxide nanoparticles (DCeE) induces stress in the brain of a susceptible animal model. Atherosclerotic prone, apolipoprotein E knockout (ApoE−/−) mice fed a high-fat diet, were exposed by inhalation to purified air (control), DE or DCeE. The stress-responsive transcription factor, activator protein-1 (AP-1), was significantly decreased in the cortical and subcortical fraction of the brain after DE exposure. The addition of nanoceria to the diesel fuel reversed this effect. The activation of another stress-related transcription factor (NF-κB) was not inhibited. AP-1 is composed of complexes of the Jun and/or Fos family of proteins. Exposure to DCeE caused c-Jun activation and this may be a mechanism by which addition of nanoceria to the fuel reversed the effect of DE exposure on AP-1 activation. This pilot study demonstrates that exposure to DE does impact the brain and addition of nanoceria may be protective. However, more extensive studies are necessary to determine how DE induced reduction of AP-1 activity and compensation by nanoceria impacts normal function of the brain.

Read More: http://informahealth...journalCode=iht


#8 Kalliste

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Posted 07 May 2015 - 06:07 PM


7.3. Noble metal oxide-based nano-antioxidants
Recent evidence indicates that several types of metal oxide
nanoparticles might themselves act as free radical scavengers and antioxidants.
One example is cerium oxide nanoparticles (CeONP). Cerium
is a rare earth metal belonging to the lanthanide series of the periodic
table. When combined with oxygen in nanoparticle formulation, cerium
oxide adopts a fluorite crystalline structure that has antioxidant properties
in vitro (Heckert et al., 2008; Korsvik et al., 2007), as shown by its
ability to prevent loss of cell viability after hydrogen peroxide (H2O2) exposure
and UV-light irradiation of normal breast cells (Tarnuzzer et al.,
2005). Nanocrystalline cerium oxide harbors some unique properties
differing fromitsmicrometer counterpart, including a blue shift in the ultraviolet
absorption spectrum, illustrating the fact that the properties of
nano-materials cannot be predicted from the bulk properties of the
same material (Tarnuzzer et al., 2005). The antioxidant properties of
CeONP appear to stem from their capacity to reversibly bind oxygen
and to shift between Ce4+ and Ce3+ states under oxidizing and reducing
conditions, thus scavenging various ROS (Esch et al., 2005). CeONPs are
reported to possess both SOD mimetic activity (generally when cerium
is oxidized: Ce4+) and catalase mimetic activity (generallywhen cerium
is reduced: Ce3+) (Heckert et al., 2008; Pirmohamed et al., 2010).
The antioxidant properties of CeONPs have been investigated in vitro
and in vivo. For example, single dose administration of cerium oxide
nanoparticles (CeONP) was shown to decrease inflammatory microglial
activation and increase longevity in D. melanogaster, as well as
protecting mixed organotypic cultures of brain cells from oxidative
damage as a result of challenge with UV light and hydrogen peroxide
(Elswaifi et al., 2009; Rzigalinski et al., 2006).
The potential neuroprotective effects of CeONP were also seen in
glutamate-induced cytotoxicity in isolated HT22 hippocampal neuronal
cells. Similarly, survival and functions of neurons isolated from adult
rats were preserved following a hydrogen peroxide insult after treatment
with CeONP (Das et al., 2007; Schubert et al., 2006).
Neuroprotective capacity of CeONP was again demonstrated in a
mouse hippocampal brain slicemodel of cerebral ischemia,whereby ischemic
cell death was reduced at doses ranging from 0.2 to 1 μg/ml
(Estevez et al., 2011). In this study, as illustrated in the transmission
electron microscopy (TEM) micrographs, it was suggested that these
protective effects were due to the proximity of ceria to the principal
sources of ROS production, i.e., mitochondria. However, the inference
has to be taken with caution because TEM micrographs are not sufficient
to fully establish a location.
CeONP also prevented any increase in the intracellular concentrations
of ROS (as measured by flow-cytometry in terms of intracellular
DCF-DA signal) in primary rat retinal cells, which normally degenerates
under long-term light exposure.More impressively, these nanoparticles
protected photoreceptor cells from loss of vision due to light-induced
degeneration in an in vivo albino rat light-damage model (Chen et al.,
An in vivo study using CeONP-treated transgenic mice expressing
high levels of the monocyte chemoattractant MCP-1, which would
normally lead to progression of cardiac dysfunction and remodeling,
showed reduced myocardial oxidative stress, inflammation, and cell

death (Niu et al., 2007). Indeed, a quantitative analysis showed that
intravenous CeO2 injections appeared to significantly suppress
peroxynitrite formation and decrease the levels of nitrating species
(measured as serum levels of total nitrated proteins) in the myocardium
of mice in comparison to the controls, thus suggesting that
treatment with CeO2 nanoparticles attenuated myocardial oxidative
Besides CeONPs, diamond nanoparticles (D-NP) exposed to the
Fenton reaction (which generates hydroxyl radicals (OH•) that promote
degradation of any organicmatter) resulted in a decrease in particle size
and formation of a large population of surface -OH groups, which could
be used for further conjugation with bioactive molecules. These D-NP
were used as a support of gold and platinum nanoparticles (b2 nmaverage
size) and the resulting material showed good biocompatibility
when using static cytometry to count human hepatoma cells (Hep3B)
and human cervical carcinoma cells (HeLa) at 24, 48, and 72 h of incubation.
Moreover, its in vitro antioxidant activity was assessed against
rotenone-induced ROS production in a hepatoma cell line using intracellular
DCF-DA fluorescence as proxy for ROS flux (Martin et al., 2010).
Another example of nano-particles acting as antioxidants was demonstrated
by Kajita et al. In this study, platinumnanoparticles, stabilized
by pectin (CP-Pt) and with an average diameter of 4.7±1.5 nm, were
found to convert H2O2 into O2 and to react with O2•− in an in vitro
test-tube assay (Kajita et al., 2007). Conversion of H2O2was determined
via a spectrophotometric method (by measuring the residual concentration
of H2O2 after a 5 minute incubation with the samples through
absorbance reading at 240 nm) while the loss of O2•− was measured
by electron spin resonance (ESR) and via inhibition of formazan formation.
CP-Pt nano-particleswere found to quench 80% of H2O2 and 60% of
O2•− at concentration of 100 μMand 200 μM, respectively (Kajita et al.,
2007). These data have been interpreted as evidence for catalase/SOD
mimetic properties and the same research group further elucidated
the possible survival benefit conferred by platinum nanoparticles.
Nano-platinum particles (nano-Pt) stabilized with Poly(N-vinyl-2-
pyrrolidone) (PVP) were introduced into a culture of C. elegans
(Kim et al., 2008). Nano-Pt at 0.5 mM was claimed to significantly
enhance (by more than 20%) the lifespan of WT N2 nematodes and
increased their resistance to oxidative stress. On the basis of similar
capabilities, also SOD/catalasemimetics like EUK-8 should also prolong
worm life, although their claimed effects on lifespan, as reported in
some papers, were difficult to reproduce. An additional experiment included
themev-1(kn1)mutant,which has a shortened lifespan thought
to be due to excessive oxidative stress. The nano-Pt at 0.25 and 0.5 mM,
extended themutant's lifespan by about 10% after exposure to paraquat
(also used in the mild mitochondrial uncoupling approaches reported
in Section 6.1), albeit the lifespan was still not comparable with wild
type. Once again, nano-Pt at 0.1 and 0.5 mM were effective in slightly
ameliorating the ROS (as measured by the emission at 510 nm of the
fluorescent probe DCF-DA, after fixed nematode samples were incubatedwith
0.4 Mparaquat for 5 h and subjected to laser scanning confocal
microscopy at an excitation of 488 nm) and providing a slight increase
in survival time. It should be noted that the same nanoparticles at a
concentration of 1 mM failed to provide lifespan extension in all
the above-reported experiments: this could be attributed to either

nano-Pt toxicity to the worms (which is still unexplored) or perhaps
even to an excessive quenching of ROS that interfered with normal
physiological functions. This result also highlights the delicate balance
between the potential benefit of nanotechnology on one side,
and the possible risks associated with nanomaterials on the other,
especially in view of their potential accumulation in the body and
their long-term effects.
To further compare the SOD and catalase activities of nano-Pt and
EUK-8, their scavenging abilities for O2•− and H2O2 were estimated in
vitro. O2•− was generated through the enzymatic reaction between
xanthine and xanthine oxidase and was quantified by its effect on
formazan formation. Loss of H2O2 was determined by a spectrophotometric
method after addition of either nano-Pt or EUK-8. By measuring
this in vitro dose-dependent quenching of O2•− and H2O2, nano-Pt
were shown to be a more potent SOD/catalase mimetic than EUK-8.
This effect seems to correlate with nano-Pt's higher ROS scavenging
ability than EUK-8. In other words, by quenching in a more effective
way H2O2, which leads to less hydroxyl radicals, they may bemore efficient
in removing ROS. A further improvement may derive from the
synthesis of nano-Pt fused with an HIV-1 TAT fusion protein
C-terminally linked to a peptide with high affinity for platinum (Kim
et al., 2010). The conjugate showed improved internalisation while
maintaining similar level of antioxidant properties at only 5 μM,
which is a hundred times lower than the concentration of nano-Pt
used in the previous experiments. This last result seems to support
the idea that proper targeting through nano-carriers paves the way
for future developments that are able to overcome current limitations
and trigger the desired effects onlywhere they are required, while minimizing
any unwanted toxicity.


#9 normalizing

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Posted 08 May 2015 - 09:58 AM

interestingly, first to reply here. but let me ask this, where do you buy this anyway?

#10 Kalliste

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Posted 10 May 2015 - 05:38 PM


(Probably not safe for human consumption but to be honest I'm not sure. We might be talking about a very small, infrequent dose)


Another one:



Also probably not safe for human consumption. I don't have time to see what reserachers did to dissolve it, it seems a bit hard from what I can remember but maybe they are overdoing it for the sake of scientific integrity.

It seems like a relatively small amount can have seriously neat effects on autophagy for instance.

#11 Kalliste

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Posted 27 May 2015 - 05:03 AM

Here is a review I dont think was posted.






Derived from quick and expedient mutations of the oxidation state

between Ce4þ and Ce3þ, CeONP has excellent catalytic and multienzyme-

mimetic properties. These make it attractive for widespread

applications, both in industry and in biosystems. At present, the

industrial applications of CeONP are well developed, whereas bioapplications

are still in their infancy. Numerous studies have reported

enzyme-like activities of CeONP, the results of which were supported

by abiotic studies in simple buffer solutions; however, they must be

demonstrated and investigated further in biological media, cells,

tissues and even animals. In addition, there are divergent biological

effects obtained with CeONP, with it being beneficial in one case and

toxic in another. Thus, the toxic mechanism should be carefully and

systematically investigated with animal models over long periods of

time, and comprehensive investigative methods must be developed. It

is also worth noting that the CeONP used in the investigations were

not consist in preparation, particle size or surface characteristic, even

though these features may have important role in CeONP’s biological

reactivity/toxicology. Unfortunately, until recently, information about

the relationships between the properties of CeONP was fragmented

and vague. Further systematic investigations are required.

Although there are still some unresolved issues and challenges, the

unique physical and chemical properties of CeONP and the achieved

significant advances of it clearly demonstrate that CeONP is a

fascinating and versatile material that is promising for numerous

industrial and biomedical applications


#12 normalizing

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Posted 27 May 2015 - 06:17 AM

i still dont know where to find this

#13 Kalliste

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Posted 27 May 2015 - 10:23 AM

It does not exist yet, well I guess you could buy the powder rather cheaply and use one of the methods detailed. Possibly you only need to sonicate it with water, hell you might only have to swish it around with a spoon for all I know. These papers are done with scientific rigor to eliminate confusion so they use all kinds of high tech filtration metods. With C60, it turned out you could do it on your own pretty much. I dont know if this is the same thing. Here are some more papers.




Researcher community showed more concerned about the impact of nao-ceria on human and environment in the last few years. Bacteria, plants, aquatic and terrestrial organisms and mammal models are extensively employed in the investigation for chemistry and toxicological assay of nano-ceria. However the findings seem difficult because of contradicting behaviors. It may either acts as antioxidant or pro-oxidant producing the reactive oxygen species (Park et al., 2008; Karakoti et al.,

2010). Further chemical species, pH, concentration and phosphate buffer may alter the behavior of nano-ceria (Dahle et al., 2014) further investigations are required.

Based on the available data, it is concluded that cerium nanomaterials toxicity seems to be little and would not be concerned when inhaled or ingested. The absence of more complete information precluded accessing the possible health effects of victimization of nano-ceria as fuel additive. Secondly, the accessible ROS modulators are short half-life, required antioxidant inhibitor molecules for every radicle scavenging. Ce-NPs act as body single particle scavenger scavenging or reducing the several free radicles through its auto-regenerative ability. So the number of applications combating the oxidative stress are numerous. This provides firm bases and evidences of bright future of Ce-NPs in the pharmaceutical of diabetes, cancer and other ROS-linked disorders. The researchers are pursuing of Ce-NPs commercial applications.

CeO-NPs are extensively used in the industry and bio-system because of antioxidative and multi-enzymatic mimetic ability. This ability is derived on the basis of quick and expedient mutation between Ce+4 and Ce+3 oxidation state. In current scenario, the industrial applications of nano-ceria are well developed and understood but the bio-applications are still in the infancy. Literature reported that the enzymatic mimetic properties are largely affected by buffer solution, biological media, cell tissue and animal internal conditions. CeO-NPs showed divergent applications which are beneficial in one situation and toxic in another. So toxic mechanism should be rigorously studied and ways of investigation must be developed. Sadly, informations regarding the biological impacts of Ce-NPs are still fragmentary and obscure and there is a dire need to be investigated systematically.




Pilot in vivo investigation of cerium oxide nanoparticles as a novel anti-obesity pharmaceutical formulation
  • aIstituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy
  • bScuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy
  • cUniversity of Pisa, Department of Clinical and Experimental Medicine, Via Roma 55, 56126 Pisa, Italy
  • dUniversity of Pisa, Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, Via Roma 55, 56126 Pisa, Italy
  • eIstituto Italiano di Tecnologia, Nanochemistry Department, Via Morego 30, 16163 Genova, Italy
  • fUniversity of Pisa, Division of Pharmacology & Toxicology, Veterinary Sciences Department, Via Livornese 1, 56122 San Piero a Grado (Pisa), Italy



Obesity is a worldwide pathological condition that strongly impairs human health, and, to date, no effective therapy against excessive fat accumulation has been found yet. Since overweight correlates with an increased oxidative stress, our aim is to investigate the antioxidant effects of cerium oxide nanoparticles (nanoceria) as a potential pharmaceutical approach for the treatment of obesity. Nanoceria were tested both in vitro and in vivo; they were proven to interfere with the adipogenic pathway by reducing the mRNA transcription of genes involved in adipogenesis, and by hindering the triglycerides accumulation in 3T3-L1 pre-adipocytes. Nanoceria, intraperitonally injected in Wistar rats, did not have appreciable toxic effects, but instead efficiently contributed in reducing the weight gain and in lowering the plasma levels of insulin, leptin, glucose and triglycerides.


Graphical abstract

Cerium oxide nanoparticles, intraperitonally injected in Wistar rats, efficiently contributed in reducing the weight gain and in lowering the plasma levels of insulin, leptin, glucose, and triglycerides, through a powerful anti-oxidant action.



Lastly, some caution although I don't completely understand this article.


Intravenous and Gastric Cerium Dioxide Nanoparticle Exposure Disrupts Microvascular Smooth Muscle Signaling

Cerium dioxide nanoparticles (CeO2 NP) hold great therapeutic potential, but the in vivo effects of non-pulmonary exposure routes are unclear. The first aim was to determine whether microvascular function is impaired after intravenous and gastric CeO2 NP exposure. The second aim was to investigate the mechanism(s) of action underlying microvascular dysfunction following CeO2 NP exposure. Rats were exposed to CeO2 NP (primary diameter: 4 ± 1 nm, surface area: 81.36 m2/g) by intratracheal instillation, intravenous injection, or gastric gavage. Mesenteric arterioles were harvested 24 h post-exposure and vascular function was assessed using an isolated arteriole preparation. Endothelium-dependent and independent function and vascular smooth muscle (VSM) signaling (soluble guanylyl cyclase [sGC] and cyclic guanosine monophosphate [cGMP]) were assessed. Reactive oxygen species (ROS) generation and nitric oxide (NO) production were analyzed. Compared with controls, endothelium-dependent and independent dilation were impaired following intravenous injection (by 61% and 45%) and gastric gavage (by 63% and 49%). However, intravenous injection resulted in greater microvascular impairment (16% and 35%) compared with gastric gavage at an identical dose (100 µg). Furthermore, sGC activation and cGMP responsiveness were impaired following pulmonary, intravenous, and gastric CeO2 NP treatment. Finally, nanoparticle exposure resulted in route-dependent, increased ROS generation and decreased NO production. These results indicate that CeO2 NP exposure route differentially impairs microvascular function, which may be mechanistically linked to decreased NO production and subsequent VSM signaling. Fully understanding the mechanisms behind CeO2 NP in vivo effects is a critical step in the continued therapeutic development of this nanoparticle.


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#14 Kalliste

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Posted 07 August 2015 - 12:05 PM


Biomed Pharmacother. 2015 Jul;73:80-6. doi: 10.1016/j.biopha.2015.05.006. Epub 2015 May 30.
Cerium oxide nanoparticles alleviate oxidative stress and decreases Nrf-2/HO-1 in D-GALN/LPS induced hepatotoxicity. Abstract

Translocation of the master regulator of antioxidant-response element-driven antioxidant gene, nuclear factor erythroid 2 (Nrf-2) from the cytoplasm into the nucleus and triggering the transcription of hemoxygenase-1 (HO-1) to counteract the oxidative stress is a key feature in D-galactoseamine and lipopolysaccharide (D-GALN/LPS) induced hepatotoxicity. We mainly aimed to study the effect of cerium oxide (CeO2) nanoparticles on Nrf-2/HO-1 pathway whereas; it has previously shown to have an antioxidant effect in liver models. Administration of CeO2 nanoparticles significantly decreased the translocation of the cytoplasmic Nrf-2 with a concomitant decrement in the gene expression of HO-1 as it reveals a powerful antioxidative effect as indicated by the significant increase in the levels of glutathione (GSH), glutathione peroxidase (GPX1), glutathione reductase (GR), superoxide dismutase (SOD) and catalase. In synchronization, a substantial decrement in the levels of inducible nitric oxide synthase (iNOS), TBARS and percentage of DNA fragmentation was established. These results were confirmed by histopathology examination which showed a severe degeneration, haemorrhages, widened sinusoids and focal leukocyte infiltration in D-GALN/LPS treatment and these features were alleviated with CeO2 administration. In conclusion, CeO2 is a potential antioxidant that can effectively decrease the translocation of the cytoplasmic Nrf-2 into the nucleus and decrease HO-1 in D-GALN/LPS induced hepatotoxicity.




Nanoscale. 2015 Jul 31. [Epub ahead of print]
Engineering the defect state and reducibility of ceria based nanoparticles for improved anti-oxidation performance.

Due to their excellent anti-oxidation performance, CeO2nanoparticles receive wide attention in pharmacological application. Deep understanding of the anti-oxidation mechanism of CeO2nanoparticles is extremely important to develop potent CeO2 nanomaterials for anti-oxidation application. Here, we report a detailed study on the anti-oxidation process of CeO2nanoparticles. The valence state and coordination structure of Ce are characterized before and after the addition of H2O2 to understand the anti-oxidation mechanism of CeO2nanoparticles. Adsorbed peroxide species are detected during the anti-oxidation process, which are responsible for the red-shifted UV-vis absorption spectra of CeO2nanoparticles. Furthermore, the coordination number of Ce in the first coordination shell slightly increased after the addition of H2O2. On the basis of these experimental results, the reactivity of coordination sites for peroxide species is considered to play a key role in the anti-oxidation performance of CeO2nanoparticles. Furthermore, we present a robust method to engineer the anti-oxidation performance of CeO2nanoparticles through the modification of the defect state and reducibility by doping with Gd3+. Improved anti-oxidation performance is also observed in cell culture, where the biocompatible CeO2-based nanoparticles can protect INS-1 cells from oxidative stress induced by H2O2, suggesting the potential application of CeO2nanoparticles in the treatment of diabetes.


Not good to inhale perhaps?



J Prev Med Public Health. 2015 May;48(3):132-41. doi: 10.3961/jpmph.15.006. Epub 2015 May 18.
Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs.

With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.


Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis.


No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05).


Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.



Also tagged with one or more of these keywords: nanoceria, autophagy, antioxidant, cerium

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